[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"_public_publisher_byId_c788a3ef-bcb4-429c-9d7c-8e62655adca3":3,"_public_publication_all{\"sortAscending\":false,\"sortField\":\"updateTime\",\"page\":0,\"size\":10,\"facet\":true,\"searchKey\":\"publisherId:c788a3ef-bcb4-429c-9d7c-8e62655adca3,\"}":108},{"code":4,"data":5,"meta":24},"SUCCESS",{"id":6,"createTime":7,"updateTime":8,"relativeEntities":9,"slug":10,"properties":11,"entityType":22,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":25,"subjectFields":26,"manageAffiliations":39,"indexDatabases":54,"url":90,"thumbnailPath":24,"statistic":91,"gsStatistic":24,"type":24,"analyzePriority":24},"c788a3ef-bcb4-429c-9d7c-8e62655adca3","2023-05-29T10:27:29.302+00:00","2025-11-21T09:57:10.615+00:00",[],"Nature-Reviews-Molecular-Cell-Biology",{"country":12,"eissn":14,"issn":16,"title":18,"introduce":20},{"VOID":13},"GB",{"VOID":15},"14710080",{"VOID":17},"14710072",{"EN":19},"Nature Reviews Molecular Cell Biology",{"EN":21},"Nature Reviews Molecular Cell Biology aims to be the premier source of reviews and commentaries for the scientific communities we serve. We strive to publish articles that are authoritative, accessible and enhanced with clearly understandable figures, tables and other display items. We want to provide an unparalleled service to authors, referees and readers, and we work hard to maximize the usefulness and impact of each article. The journal publishes Reviews, Perspectives, Comments and Research Highlights relevant to molecular and cell biologists, with our broad scope ensuring that the articles we publish reach the widest possible audience.","PUBLISHER","PENDING",null,0,[27,33],{"id":28,"createTime":24,"updateTime":24,"relativeEntities":29,"label":30,"description":32,"parentId":24,"standard":24,"scholarHubFieldId":24},"131e254e-0b02-478f-aa3e-0b27d8c7b9d1",[],{"EN":31},"Cell Biology",{},{"id":34,"createTime":24,"updateTime":24,"relativeEntities":35,"label":36,"description":38,"parentId":24,"standard":24,"scholarHubFieldId":24},"e28d6c37-225c-41f9-829b-a62e54bf45c7",[],{"EN":37},"Molecular Biology",{},[40,47],{"id":41,"createTime":24,"updateTime":24,"relativeEntities":42,"slug":24,"properties":43,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":46,"statistic":24},"b134a19f-d595-49fa-bd59-70d90fa3a3b3",[],{"title":44},{"EN":45},"NATURE PORTFOLIO",[],{"id":48,"createTime":24,"updateTime":24,"relativeEntities":49,"slug":24,"properties":50,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":53,"statistic":24},"ae54b068-a7dd-4746-b752-b7b24439de47",[],{"title":51},{"EN":52},"Nature Publishing Group",[],[55,72],{"id":56,"indexDatabase":57,"url":69,"indexYears":24,"academicFieldIds":70,"indexDatabaseRanking":24},"5b27a000-e2d3-4947-a584-fa72cd936824",{"id":58,"createTime":24,"updateTime":24,"relativeEntities":59,"label":60,"description":62,"key":65,"publicationTags":66,"standard":24},"a4921856-b128-4d9f-8f1f-e80813d3bbd4",[],{"EN":61,"VI":61},"ISI\u002FSCIE - Science Citation Index Expanded",{"EN":63,"VI":64},"SCIE database","Cơ sở dữ liệu SCIE","scie",[67,68],"SCIE","ISI","https:\u002F\u002Fmjl.clarivate.com\u002Fsearch-results?issn=1471-0072",[71],"8eb75d88-0c7a-497c-a346-e729afc75040",{"id":73,"indexDatabase":74,"url":84,"indexYears":85,"academicFieldIds":86,"indexDatabaseRanking":89},"29311d27-f00f-4994-83d2-9ef6dd4b857f",{"id":75,"createTime":24,"updateTime":24,"relativeEntities":76,"label":77,"description":79,"key":81,"publicationTags":82,"standard":24},"3c7051d4-eb7d-4c57-a56b-36fc74c5d1e9",[],{"EN":78,"VI":78},"Scopus - Elsevier",{"EN":78,"VI":80},"Cơ sở dữ liệu Scopus thuộc Elsevier","scopus",[83],"SCOPUS","https:\u002F\u002Fwww.scopus.com\u002Fsourceid\u002F20315","2000-2025",[87,88],"0404956d-7818-4510-b67a-db80799a6ec0","d2139bd1-2fdb-481b-a416-9c30dd0cc173","SCOPUS__Q1","https:\u002F\u002Fwww.nature.com\u002Fnrm\u002F",{"impactFactor":25,"impactFactorByYear":92,"i10Index":97,"i10IndexLast5Year":25,"totalPublication":97,"totalPublicationByYear":98,"totalCitation":100,"totalCitationByYear":101,"totalCitationPerPublication":106,"totalCitationPerPublicationByYear":107,"hindexLast5Year":97,"hindex":97},{"2016":93,"2017":94,"2019":95,"2020":96},34,51,118,183,4,{"2007":99,"2009":99,"2015":99,"2018":99},1,4146,{"2007":102,"2009":103,"2015":104,"2018":105},1176,1149,524,1297,1036.5,{"2007":102,"2009":103,"2015":104,"2018":105},{"meta":109,"data":111},{"total":110},"328",[112,410,953,1662,2032,3210,3902,4584,5053,5863],{"id":113,"createTime":114,"updateTime":115,"relativeEntities":116,"slug":117,"properties":118,"entityType":131,"verifyStatus":132,"verifyTime":114,"verifyNote":133,"languages":134,"translateLanguages":24,"viewCount":25,"primaryUrl":136,"fullTextUrl":24,"authors":137,"publicationType":174,"publisherRelationship":175,"citationCount":230,"citationInfo":231,"publishDate":246,"publishYear":232,"citationAnalyzeStatus":247,"lastCitationAnalyze":115,"indexDatabases":248,"openAccess":24,"references":249,"isForceReanalyzing":409},"201fbd9a-4c9c-4cff-8171-90d938546d63","2024-11-28T00:39:17.725+00:00","2026-08-16T16:37:40.631+00:00",[],"High-throughput-fluorescence-microscopy-for-systems-biology",{"openalex":119,"mag":121,"title":123,"gsPaper":125,"pm":127,"doi":129},{"VOID":120},"W2158706178",{"VOID":122},"2158706178",{"EN":124},"High-throughput fluorescence microscopy for systems biology",{"VOID":126},"[]",{"VOID":128},"16850035",{"VOID":130},"10.1038\u002Fnrm1979","PUBLICATION","VERIFIED","Auto Verify",[135],"EN","https:\u002F\u002Fwww.nature.com\u002Farticles\u002Fnrm1979",[138,157],{"id":139,"sortIndex":25,"researcher":24,"roles":140,"affiliations":141,"properties":150,"displayName":154,"givenName":24,"familyName":24},"c98c85f0-7dab-402d-9f98-86b8867664c1",[],[142],{"id":143,"sortIndex":25,"affiliation":144,"properties":24},"e45a074a-c3d9-49a5-ae11-d822f08c6bcd",{"id":143,"createTime":24,"updateTime":24,"relativeEntities":145,"slug":24,"properties":146,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":149,"statistic":24},[],{"title":147},{"EN":148},"Cell Biology\u002FBiophysics Unit,",[],{"orcid":151,"title":153,"openalex":155},{"VOID":152},"https:\u002F\u002Forcid.org\u002F0000-0002-9762-3583",{"EN":154},"Rainer Pepperkok",{"VOID":156},"A5017298007",{"id":158,"sortIndex":99,"researcher":24,"roles":159,"affiliations":160,"properties":167,"displayName":171,"givenName":24,"familyName":24},"b489a369-bb21-44b8-abbe-6a2497ac03cd",[],[161],{"id":143,"sortIndex":25,"affiliation":162,"properties":24},{"id":143,"createTime":24,"updateTime":24,"relativeEntities":163,"slug":24,"properties":164,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":166,"statistic":24},[],{"title":165},{"EN":148},[],{"orcid":168,"title":170,"openalex":172},{"VOID":169},"https:\u002F\u002Forcid.org\u002F0000-0001-5909-701X",{"EN":171},"Jan Ellenberg",{"VOID":173},"A5043267985","ARTICLE",{"url":24,"publisher":176,"properties":223},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":177,"slug":10,"properties":178,"entityType":22,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":25,"subjectFields":183,"manageAffiliations":192,"indexDatabases":203,"url":90,"thumbnailPath":24,"statistic":218,"gsStatistic":24,"type":24,"analyzePriority":24},[],{"country":179,"eissn":180,"issn":181,"title":182},{"VOID":13},{"VOID":15},{"VOID":17},{"EN":19},[184,188],{"id":28,"createTime":24,"updateTime":24,"relativeEntities":185,"label":186,"description":187,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":31},{},{"id":34,"createTime":24,"updateTime":24,"relativeEntities":189,"label":190,"description":191,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":37},{},[193,198],{"id":41,"createTime":24,"updateTime":24,"relativeEntities":194,"slug":24,"properties":195,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":197,"statistic":24},[],{"title":196},{"EN":45},[],{"id":48,"createTime":24,"updateTime":24,"relativeEntities":199,"slug":24,"properties":200,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":202,"statistic":24},[],{"title":201},{"EN":52},[],[204,211],{"id":56,"indexDatabase":205,"url":69,"indexYears":24,"academicFieldIds":210,"indexDatabaseRanking":24},{"id":58,"createTime":24,"updateTime":24,"relativeEntities":206,"label":207,"description":208,"key":65,"publicationTags":209,"standard":24},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":212,"url":84,"indexYears":85,"academicFieldIds":217,"indexDatabaseRanking":89},{"id":75,"createTime":24,"updateTime":24,"relativeEntities":213,"label":214,"description":215,"key":81,"publicationTags":216,"standard":24},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88],{"impactFactor":25,"impactFactorByYear":219,"i10Index":97,"i10IndexLast5Year":25,"totalPublication":97,"totalPublicationByYear":220,"totalCitation":100,"totalCitationByYear":221,"totalCitationPerPublication":106,"totalCitationPerPublicationByYear":222,"hindexLast5Year":97,"hindex":97},{"2016":93,"2017":94,"2019":95,"2020":96},{"2007":99,"2009":99,"2015":99,"2018":99},{"2007":102,"2009":103,"2015":104,"2018":105},{"2007":102,"2009":103,"2015":104,"2018":105},{"issue":224,"pages":226,"volume":228},{"VOID":225},"9",{"VOID":227},"690-696",{"VOID":229},"7",419,{"total":230,"publishYear":232,"statisticByYear":233},2006,{"2012":234,"2013":235,"2014":236,"2015":237,"2016":238,"2017":239,"2018":240,"2019":241,"2020":242,"2021":243,"2022":240,"2023":244,"2024":245},30,32,39,17,20,24,15,18,13,14,16,6,"2006-09-01","ERROR_IN_GET_PLATFORM_ID",[67,89],[250,254,258,262,266,270,274,278,282,286,290,294,298,302,306,310,313,317,321,325,329,333,336,339,343,346,349,353,357,361,365,369,373,377,381,385,389,393,397,401,405],{"id":24,"text":251,"url":24,"identifiers":252},"International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 431, 931?945 (2004).",{"doi":253},"10.1038\u002Fnature03001",{"id":24,"text":255,"url":24,"identifiers":256},"Lippincott-Schwartz, J. & Patterson, G. H. Development and use of fluorescent protein markers in living cells. Science 300, 87?91 (2003).",{"doi":257},"10.1126\u002Fscience.1082520",{"id":24,"text":259,"url":24,"identifiers":260},"Chudakov, D. M., Lukyanov, S. & Lukyanov, K. A. Fluorescent proteins as a toolkit for in vivo imaging. Trends Biotechnol. 23, 605?613 (2005).",{"doi":261},"10.1016\u002Fj.tibtech.2005.10.005",{"id":24,"text":263,"url":24,"identifiers":264},"Tsien, R. Y. Building and breeding molecules to spy on cells and tumors. FEBS Lett. 579, 927?932 (2005).",{"doi":265},"10.1016\u002Fj.febslet.2004.11.025",{"id":24,"text":267,"url":24,"identifiers":268},"Mayer, T. U. et al. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 286, 971?974 (1999).",{"doi":269},"10.1126\u002Fscience.286.5441.971",{"id":24,"text":271,"url":24,"identifiers":272},"Perlman, Z. E. et al. Multidimensional drug profiling by automated microscopy. Science 306, 1194?1198 (2004).",{"doi":273},"10.1126\u002Fscience.1100709",{"id":24,"text":275,"url":24,"identifiers":276},"Wheeler, D. B., Carpenter, A. E. & Sabatini, D. M. Cell microarrays and RNA interference chip away at gene function. Nature Genet. 37 (Suppl. 1), S25?S30 (2005).",{"doi":277},"10.1038\u002Fng1560",{"id":24,"text":279,"url":24,"identifiers":280},"Starkuviene, V. et al. High-content screening microscopy identifies novel proteins with a putative role in secretory membrane traffic. Genome Res. 14, 1948?1956 (2004).",{"doi":281},"10.1101\u002Fgr.2658304",{"id":24,"text":283,"url":24,"identifiers":284},"Pelkmans, L. et al. Genome-wide analysis of human kinases in clathrin- and caveolae\u002Fraft-mediated endocytosis. Nature 463, 78?86 (2005).",{"doi":285},"10.1038\u002Fnature03571",{"id":24,"text":287,"url":24,"identifiers":288},"Sonnichsen, B. et al. Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434, 462?469 (2005).",{"doi":289},"10.1038\u002Fnature03353",{"id":24,"text":291,"url":24,"identifiers":292},"Mitchison, T. J. Small-molecule screening and profiling by using automated microscopy. Chembiochem 6, 33?39 (2005).",{"doi":293},"10.1002\u002Fcbic.200400272",{"id":24,"text":295,"url":24,"identifiers":296},"Abraham, V. C., Taylor, D. L. & Haskins, J. R. High content screening applied to large-scale cell biology. Trends Biotechnol. 22, 15?22 (2004).",{"doi":297},"10.1016\u002Fj.tibtech.2003.10.012",{"id":24,"text":299,"url":24,"identifiers":300},"Patterson, G. H. & Lippincott-Schwartz, J. Selective photolabeling of proteins using photoactivatable GFP. Methods 32, 445?450 (2004).",{"doi":301},"10.1016\u002Fj.ymeth.2003.10.006",{"id":24,"text":303,"url":24,"identifiers":304},"Meyer, T. & Teruel, M. N. Fluorescence imaging of signaling networks. Trends Cell Biol. 13, 101?106 (2003).",{"doi":305},"10.1016\u002FS0962-8924(02)00040-5",{"id":24,"text":307,"url":24,"identifiers":308},"Bastiaens, P. I. & Pepperkok, R. Observing proteins in their natural habitat: the living cell. Trends Biochem. Sci. 25, 631?637 (2000).",{"doi":309},"10.1016\u002FS0968-0004(00)01714-X",{"id":24,"text":311,"url":24,"identifiers":312},"Miyawaki, A., Nagai, T. & Mizuno, H. Engineering fluorescent proteins. Adv. Biochem. Eng Biotechnol. 95, 1?15 (2005).",{},{"id":24,"text":314,"url":24,"identifiers":315},"Wouters, F. S., Verveer, P. J. & Bastiaens, P. I. Imaging biochemistry inside cells. Trends Cell Biol. 11, 203?211 (2001).",{"doi":316},"10.1016\u002FS0962-8924(01)01982-1",{"id":24,"text":318,"url":24,"identifiers":319},"Phizicky, E., Bastiaens, P. I., Zhu, H., Snyder, M. & Fields, S. Protein analysis on a proteomic scale. Nature 422, 208?215 (2003).",{"doi":320},"10.1038\u002Fnature01512",{"id":24,"text":322,"url":24,"identifiers":323},"Miyawaki, A. Innovations in the imaging of brain functions using fluorescent proteins. Neuron 48, 189?199 (2005).",{"doi":324},"10.1016\u002Fj.neuron.2005.10.003",{"id":24,"text":326,"url":24,"identifiers":327},"Rabut, G. & Ellenberg, J. Automatic real-time three-dimensional cell tracking by fluorescence microscopy. J. Microsc. 216, 131?137 (2004).",{"doi":328},"10.1111\u002Fj.0022-2720.2004.01404.x",{"id":24,"text":330,"url":24,"identifiers":331},"Liebel, U. et al. A microscope-based screening platform for large-scale functional protein analysis in intact cells. FEBS Lett. 554, 394?398 (2003).",{"doi":332},"10.1016\u002FS0014-5793(03)01197-9",{"id":24,"text":334,"url":24,"identifiers":335},"Herman, B., Krishnan, R. V. & Centonze, V. E. Microscopic analysis of fluorescence resonance energy transfer (FRET). Methods Mol. Biol. 261, 351?370 (2004).",{},{"id":24,"text":337,"url":24,"identifiers":338},"Rabut, G. & Ellenberg, J. in Live Cell Imaging: A Laboratory Manual (eds Goldman, R. D. & Spector, D. L.) 101?127 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2005).",{},{"id":24,"text":340,"url":24,"identifiers":341},"Sprague, B. L. & McNally, J. G. FRAP analysis of binding: proper and fitting. Trends Cell Biol. 15, 84?91 (2005).",{"doi":342},"10.1016\u002Fj.tcb.2004.12.001",{"id":24,"text":344,"url":24,"identifiers":345},"Lippincott-Schwartz, J., Altan-Bonnet, N. & Patterson, G. H. Photobleaching and photoactivation: following protein dynamics in living cells. Nature Cell Biol. 5(Suppl.), S7?S14 (2003).",{},{"id":24,"text":347,"url":24,"identifiers":348},"Kohl, T. & Schwille, P. Fluorescence correlation spectroscopy with autofluorescent proteins. Adv. Biochem. Eng. Biotechnol. 95, 107?142 (2005).",{},{"id":24,"text":350,"url":24,"identifiers":351},"Pramanik, A. Ligand?receptor interactions in live cells by fluorescence correlation spectroscopy. Curr. Pharm. Biotechnol. 5, 205?212 (2004).",{"doi":352},"10.2174\u002F1389201043377002",{"id":24,"text":354,"url":24,"identifiers":355},"Conrad, C. et al. Automatic identification of subcellular phenotypes on human cell arrays. Genome Res. 14, 1130?1136 (2004).",{"doi":356},"10.1101\u002Fgr.2383804",{"id":24,"text":358,"url":24,"identifiers":359},"Hu, Y. & Murphy, R. F. Automated interpretation of subcellular patterns from immunofluorescence microscopy. J. Immunol. Methods 290, 93?105 (2004).",{"doi":360},"10.1016\u002Fj.jim.2004.04.011",{"id":24,"text":362,"url":24,"identifiers":363},"Huang, K. & Murphy, R. F. Boosting accuracy of automated classification of fluorescence microscope images for location proteomics. BMC Bioinformatics 5, 78 (2004).",{"doi":364},"10.1186\u002F1471-2105-5-78",{"id":24,"text":366,"url":24,"identifiers":367},"Neumann, B. et al. High-throughput RNAi screening by time-lapse imaging of live human cells. Nature Methods 3, 385?390 (2006).",{"doi":368},"10.1038\u002Fnmeth876",{"id":24,"text":370,"url":24,"identifiers":371},"Simpson, J. C., Neubrand, V. E., Wiemann, S. & Pepperkok, R. Illuminating the human genome. Histochem. Cell Biol. 115, 23?29 (2001).",{"doi":372},"10.1007\u002Fs004180000236",{"id":24,"text":374,"url":24,"identifiers":375},"Wiemann, S. et al. cDNAs for functional genomics and proteomics: the German Consortium. C. R. Biol. 326, 1003?1009 (2003).",{"doi":376},"10.1016\u002Fj.crvi.2003.09.036",{"id":24,"text":378,"url":24,"identifiers":379},"Wu, J. Q. & Pollard, T. D. Counting cytokinesis proteins globally and locally in fission yeast. Science 310, 310?314 (2005).",{"doi":380},"10.1126\u002Fscience.1113230",{"id":24,"text":382,"url":24,"identifiers":383},"Bork, P. & Serrano, L. Towards cellular systems in 4D. Cell 121, 507?509 (2005).",{"doi":384},"10.1016\u002Fj.cell.2005.05.001",{"id":24,"text":386,"url":24,"identifiers":387},"Blake, R. A. Cellular screening assays using fluorescence microscopy. Curr. Opin. Pharmacol. 1, 533?539 (2001).",{"doi":388},"10.1016\u002FS1471-4892(01)00092-3",{"id":24,"text":390,"url":24,"identifiers":391},"Yarrow, J. C., Feng, Y., Perlman, Z. E., Kirchhausen, T. & Mitchison, T. J. Phenotypic screening of small molecule libraries by high throughput cell imaging. Comb. Chem. High Throughput Screen. 6, 279?286 (2003).",{"doi":392},"10.2174\u002F138620703106298527",{"id":24,"text":394,"url":24,"identifiers":395},"Keller, P., Toomre, D., Diaz, E., White, J. & Simons, K. Multicolour imaging of post-Golgi sorting and trafficking in live cells. Nature Cell Biol. 3, 140?149 (2001).",{"doi":396},"10.1038\u002F35055042",{"id":24,"text":398,"url":24,"identifiers":399},"Ziauddin, J. & Sabatini, D. M. Microarrays of cells expressing defined cDNAs. Nature 411, 107?110 (2001).",{"doi":400},"10.1038\u002F35075114",{"id":24,"text":402,"url":24,"identifiers":403},"Pawley, J. B. (ed.) Handbook of Biological Confocal microscopy 2nd edn (Plenum Press, New York, 1995).",{"doi":404},"10.1007\u002F978-1-4757-5348-6",{"id":24,"text":406,"url":24,"identifiers":407},"Moffat, J. et al. A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 124, 1283?1298 (2006).",{"doi":408},"10.1016\u002Fj.cell.2006.01.040",false,{"id":411,"createTime":412,"updateTime":413,"relativeEntities":414,"slug":415,"properties":416,"entityType":131,"verifyStatus":132,"verifyTime":412,"verifyNote":133,"languages":429,"translateLanguages":24,"viewCount":25,"primaryUrl":430,"fullTextUrl":24,"authors":431,"publicationType":174,"publisherRelationship":474,"citationCount":529,"citationInfo":530,"publishDate":539,"publishYear":531,"citationAnalyzeStatus":23,"lastCitationAnalyze":540,"indexDatabases":541,"openAccess":24,"references":542,"isForceReanalyzing":409},"1869c159-0939-48dc-8160-331e04f633ab","2024-10-07T15:47:17.649+00:00","2026-07-20T12:24:53.964+00:00",[],"Lipid-traffic-floppy-drives-and-a-superhighway",{"openalex":417,"mag":419,"title":421,"gsPaper":423,"pm":425,"doi":427},{"VOID":418},"W2133529176",{"VOID":420},"2133529176",{"EN":422},"Lipid traffic: floppy drives and a superhighway",{"VOID":424},"[\"4794816208307050552\"]",{"VOID":426},"15738987",{"VOID":428},"10.1038\u002Fnrm1591",[135],"https:\u002F\u002Fwww.nature.com\u002Farticles\u002Fnrm1591",[432,453],{"id":433,"sortIndex":25,"researcher":24,"roles":434,"affiliations":435,"properties":444,"displayName":448,"givenName":24,"familyName":24},"b9421d18-cd87-4833-a4d8-370d6e468127",[],[436],{"id":437,"sortIndex":25,"affiliation":438,"properties":24},"e88fe41a-32d3-429b-90c3-c1da33a31336",{"id":437,"createTime":24,"updateTime":24,"relativeEntities":439,"slug":24,"properties":440,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":443,"statistic":24},[],{"title":441},{"EN":442},"Department of Membrane Enzymology, Institute of Biomembranes, Utrecht University, Padualaan 8, Utrecht, The Netherlands",[],{"orcid":445,"title":447,"gsAuthor":449,"openalex":451},{"VOID":446},"https:\u002F\u002Forcid.org\u002F0000-0001-8912-1586",{"EN":448},"Joost C. M. Holthuis",{"VOID":450},"[\"Nz6V_ngAAAAJ\"]",{"VOID":452},"A5004434143",{"id":454,"sortIndex":99,"researcher":24,"roles":455,"affiliations":456,"properties":465,"displayName":469,"givenName":24,"familyName":24},"5de1d133-10ee-4cf6-bd89-aeeb6eacba32",[],[457],{"id":458,"sortIndex":25,"affiliation":459,"properties":24},"90d13531-1be5-4561-acdc-ca9f1e8bd1dc",{"id":458,"createTime":24,"updateTime":24,"relativeEntities":460,"slug":24,"properties":461,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":464,"statistic":24},[],{"title":462},{"EN":463},"Department of Cell Biology, Institute of Ophthalmology, London, UK",[],{"orcid":466,"title":468,"gsAuthor":470,"openalex":472},{"VOID":467},"https:\u002F\u002Forcid.org\u002F0000-0002-7231-0775",{"EN":469},"Tim P. Levine",{"VOID":471},"[\"KfWRv9gAAAAJ\"]",{"VOID":473},"A5045167388",{"url":24,"publisher":475,"properties":522},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":476,"slug":10,"properties":477,"entityType":22,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":25,"subjectFields":482,"manageAffiliations":491,"indexDatabases":502,"url":90,"thumbnailPath":24,"statistic":517,"gsStatistic":24,"type":24,"analyzePriority":24},[],{"country":478,"eissn":479,"issn":480,"title":481},{"VOID":13},{"VOID":15},{"VOID":17},{"EN":19},[483,487],{"id":28,"createTime":24,"updateTime":24,"relativeEntities":484,"label":485,"description":486,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":31},{},{"id":34,"createTime":24,"updateTime":24,"relativeEntities":488,"label":489,"description":490,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":37},{},[492,497],{"id":41,"createTime":24,"updateTime":24,"relativeEntities":493,"slug":24,"properties":494,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":496,"statistic":24},[],{"title":495},{"EN":45},[],{"id":48,"createTime":24,"updateTime":24,"relativeEntities":498,"slug":24,"properties":499,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":501,"statistic":24},[],{"title":500},{"EN":52},[],[503,510],{"id":56,"indexDatabase":504,"url":69,"indexYears":24,"academicFieldIds":509,"indexDatabaseRanking":24},{"id":58,"createTime":24,"updateTime":24,"relativeEntities":505,"label":506,"description":507,"key":65,"publicationTags":508,"standard":24},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":511,"url":84,"indexYears":85,"academicFieldIds":516,"indexDatabaseRanking":89},{"id":75,"createTime":24,"updateTime":24,"relativeEntities":512,"label":513,"description":514,"key":81,"publicationTags":515,"standard":24},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88],{"impactFactor":25,"impactFactorByYear":518,"i10Index":97,"i10IndexLast5Year":25,"totalPublication":97,"totalPublicationByYear":519,"totalCitation":100,"totalCitationByYear":520,"totalCitationPerPublication":106,"totalCitationPerPublicationByYear":521,"hindexLast5Year":97,"hindex":97},{"2016":93,"2017":94,"2019":95,"2020":96},{"2007":99,"2009":99,"2015":99,"2018":99},{"2007":102,"2009":103,"2015":104,"2018":105},{"2007":102,"2009":103,"2015":104,"2018":105},{"issue":523,"pages":525,"volume":527},{"VOID":524},"3",{"VOID":526},"209-220",{"VOID":528},"6",472,{"total":529,"publishYear":531,"statisticByYear":532},2005,{"2012":533,"2013":93,"2014":534,"2015":534,"2016":535,"2017":536,"2018":237,"2019":240,"2020":244,"2021":536,"2022":537,"2023":240,"2024":538},23,21,25,19,12,8,"2005-03-01","2026-07-20T12:24:53.963+00:00",[67,89],[543,547,551,555,559,563,567,571,575,579,583,587,591,595,599,603,607,611,615,619,623,627,631,635,639,643,647,651,655,659,663,667,671,675,679,683,687,691,695,699,703,707,711,715,719,723,727,731,735,739,743,747,751,755,758,762,766,770,774,778,782,786,790,794,798,802,806,810,814,818,822,826,830,834,838,842,846,850,854,858,862,866,870,874,878,882,886,890,894,898,902,906,910,914,917,921,925,929,933,937,941,945,949],{"id":24,"text":544,"url":24,"identifiers":545},"Schekman, R. Merging cultures in the study of membrane traffic. Nature Cell Biol. 6, 483–486 (2004).",{"doi":546},"10.1038\u002Fncb0604-483",{"id":24,"text":548,"url":24,"identifiers":549},"Murase, K. et al. Ultrafine membrane compartments for molecular diffusion as revealed by single molecule techniques. Biophys. J. 86, 4075–4093 (2004).",{"doi":550},"10.1529\u002Fbiophysj.103.035717",{"id":24,"text":552,"url":24,"identifiers":553},"Irvine, R. Inositol lipids: to PHix or not to PHix? Curr. Biol. 14, R308–R310 (2004).",{"doi":554},"10.1016\u002Fj.cub.2004.03.051",{"id":24,"text":556,"url":24,"identifiers":557},"Kornberg, R. D. & McConnell, H. M. Inside–outside transitions of phospholipids in vesicle membranes. Biochemistry 10, 1111–1120 (1971).",{"doi":558},"10.1021\u002Fbi00783a003",{"id":24,"text":560,"url":24,"identifiers":561},"Bai, J. & Pagano, R. E. Measurement of spontaneous transfer and transbilayer movement of BODIPY-labeled lipids in lipid vesicles. Biochemistry 36, 8840–8848 (1997).",{"doi":562},"10.1021\u002Fbi970145r",{"id":24,"text":564,"url":24,"identifiers":565},"Bretscher, M. S. Membrane structure: some general principles. Science 181, 622–629 (1973).",{"doi":566},"10.1126\u002Fscience.181.4100.622",{"id":24,"text":568,"url":24,"identifiers":569},"Bishop, W. R. & Bell, R. M. Assembly of the endoplasmic reticulum phospholipid bilayer: the phosphatidylcholine transporter. Cell 42, 51–60 (1985). Using a short-chain lipid analogue, the authors discover a fast transport system for PC in rat liver microsomes that is saturable and sensitive to protein-modifying agents.",{"doi":570},"10.1016\u002FS0092-8674(85)80100-8",{"id":24,"text":572,"url":24,"identifiers":573},"Buton, X., Morrot, G., Fellmann, P. & Seigneuret, M. Ultrafast glycerophospholipid-selective transbilayer motion mediated by a protein in the endoplasmic reticulum membrane. J. Biol. Chem. 271, 6651–6657 (1996).",{"doi":574},"10.1074\u002Fjbc.271.12.6651",{"id":24,"text":576,"url":24,"identifiers":577},"Seigneuret, M. & Devaux, P. F. ATP-dependent asymmetric distribution of spin-labeled phospholipids in the erythrocyte membrane: relation to shape changes. Proc. Natl Acad. Sci. USA 81, 3751–3755 (1984).",{"doi":578},"10.1073\u002Fpnas.81.12.3751",{"id":24,"text":580,"url":24,"identifiers":581},"Daleke, D. L. Regulation of transbilayer plasma membrane phospholipid asymmetry. J. Lipid Res. 44, 233–242 (2003).",{"doi":582},"10.1194\u002Fjlr.R200019-JLR200",{"id":24,"text":584,"url":24,"identifiers":585},"Fadok, V. A. et al. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405, 85–90 (2000).",{"doi":586},"10.1038\u002F35011084",{"id":24,"text":588,"url":24,"identifiers":589},"McLean, L. R. & Phillips, M. C. Kinetics of phosphatidylcholine and lysophosphatidylcholine exchange between unilamellar vesicles. Biochemistry 23, 4624–4630 (1984).",{"doi":590},"10.1021\u002Fbi00315a017",{"id":24,"text":592,"url":24,"identifiers":593},"Voelker, D. R. New perspectives on the regulation of intermembrane glycerophospholipid traffic. J. Lipid Res. 44, 441–449 (2003).",{"doi":594},"10.1194\u002Fjlr.R200020-JLR200",{"id":24,"text":596,"url":24,"identifiers":597},"Vance, J. E. Phospholipid synthesis in a membrane fraction associated with mitochondria. J. Biol. Chem. 265, 7248–7256 (1990).",{"doi":598},"10.1016\u002FS0021-9258(19)39106-9",{"id":24,"text":600,"url":24,"identifiers":601},"Kaplan, M. R. & Simoni, R. D. Intracellular transport of phosphatidylcholine to the plasma membrane. J. Cell Biol. 101, 441–445 (1985).",{"doi":602},"10.1083\u002Fjcb.101.2.441",{"id":24,"text":604,"url":24,"identifiers":605},"Gnamusch, E., Kalaus, C., Hrastnik, C., Paltauf, F. & Daum, G. Transport of phospholipids between subcellular membranes of wild-type yeast cells and of the phosphatidylinositol transfer protein-deficient strain Saccharomyces cerevisiae sec14. Biochim. Biophys. Acta 1111, 120–126 (1992).",{"doi":606},"10.1016\u002F0005-2736(92)90281-P",{"id":24,"text":608,"url":24,"identifiers":609},"Sleight, R. G. & Pagano, R. E. Rapid appearance of newly synthesized phosphatidylethanolamine at the plasma membrane. J. Biol. Chem. 258, 9050–9058 (1983).",{"doi":610},"10.1016\u002FS0021-9258(17)44630-8",{"id":24,"text":612,"url":24,"identifiers":613},"Funato, K. & Riezman, H. Vesicular and nonvesicular transport of ceramide from ER to the Golgi apparatus in yeast. J. Cell Biol. 155, 949–959 (2001).",{"doi":614},"10.1083\u002Fjcb.200105033",{"id":24,"text":616,"url":24,"identifiers":617},"Hanada, K. et al. Molecular machinery for non-vesicular trafficking of ceramide. Nature 426, 803–809 (2003). Identifies a ceramide transporter in mammalian cells that contains a StART domain that is specific for ceramide, as well as targeting domains for the ER and Golgi.",{"doi":618},"10.1038\u002Fnature02188",{"id":24,"text":620,"url":24,"identifiers":621},"Bankaitis, V. A., Aitken, J. R., Cleves, A. E. & Dowhan, W. An essential role for a phospholipid transfer protein in yeast Golgi function. Nature 347, 561–562 (1990).",{"doi":622},"10.1038\u002F347561a0",{"id":24,"text":624,"url":24,"identifiers":625},"Whatmore, J., Wiedemann, C., Somerharju, P., Swigart, P. & Cockcroft, S. Resynthesis of phosphatidylinositol in permeabilized neutrophils following phospholipase Cβ activation: transport of the intermediate, phosphatidic acid, from the plasma membrane to the endoplasmic reticulum for phosphatidylinositol resynthesis is not dependent on soluble lipid carriers or vesicular transport. Biochem. J. 341, 435–444 (1999).",{"doi":626},"10.1042\u002Fbj3410435",{"id":24,"text":628,"url":24,"identifiers":629},"Puri, V. et al. Sphingolipid storage induces accumulation of intracellular cholesterol by stimulating SREBP-1 cleavage. J. Biol. Chem. 278, 20961–20970 (2003).",{"doi":630},"10.1074\u002Fjbc.M300304200",{"id":24,"text":632,"url":24,"identifiers":633},"McConnell, H. M. & Vrljic, M. Liquid–liquid immiscibility in membranes. Annu. Rev. Biophys. Biomol. Struct. 32, 469–492 (2003).",{"doi":634},"10.1146\u002Fannurev.biophys.32.110601.141704",{"id":24,"text":636,"url":24,"identifiers":637},"Malathi, K. et al. Mutagenesis of the putative sterol-sensing domain of yeast Niemann Pick C-related protein reveals a primordial role in subcellular sphingolipid distribution. J. Cell Biol. 164, 547–556 (2004).",{"doi":638},"10.1083\u002Fjcb.200310046",{"id":24,"text":640,"url":24,"identifiers":641},"Burger, K. N., van der Bijl, P. & van Meer, G. Topology of sphingolipid galactosyltransferases in ER and Golgi: transbilayer movement of monohexosyl sphingolipids is required for higher glycosphingolipid biosynthesis. J. Cell Biol. 133, 15–28 (1996).",{"doi":642},"10.1083\u002Fjcb.133.1.15",{"id":24,"text":644,"url":24,"identifiers":645},"Huitema, K., Van Den Dikkenberg, J., Brouwers, J. F. & Holthuis, J. C. Identification of a family of animal sphingomyelin synthases. EMBO J. 23, 33–44 (2004).",{"doi":646},"10.1038\u002Fsj.emboj.7600034",{"id":24,"text":648,"url":24,"identifiers":649},"Buton, X. et al. Transbilayer movement of monohexosylsphingolipids in endoplasmic reticulum and Golgi membranes. Biochemistry 41, 13106–13115 (2002).",{"doi":650},"10.1021\u002Fbi020385t",{"id":24,"text":652,"url":24,"identifiers":653},"Brugger, B. et al. Evidence for segregation of sphingomyelin and cholesterol during formation of COPI-coated vesicles. J. Cell Biol. 151, 507–518 (2000).",{"doi":654},"10.1083\u002Fjcb.151.3.507",{"id":24,"text":656,"url":24,"identifiers":657},"Baumgart, T., Hess, S. T. & Webb, W. W. Imaging coexisting fluid domains in biomembrane models coupling curvature and line tension. Nature 425, 821–824 (2003). This high-resolution fluorescence-imaging study on model membranes shows how lipid immiscibility and domain formation are coupled to membrane-budding and -fission events.",{"doi":658},"10.1038\u002Fnature02013",{"id":24,"text":660,"url":24,"identifiers":661},"Munro, S. Lipid rafts: elusive or illusive? Cell 115, 377–388 (2003). A critical assessment of the experimental evidence for the existence of lipid microdomains in cellular membranes.",{"doi":662},"10.1016\u002FS0092-8674(03)00882-1",{"id":24,"text":664,"url":24,"identifiers":665},"Schneiter, R. et al. Electrospray ionization tandem mass spectrometry (ESI–MS\u002FMS) analysis of the lipid molecular species composition of yeast subcellular membranes reveals acyl chain-based sorting\u002Fremodeling of distinct molecular species en route to the plasma membrane. J. Cell Biol. 146, 741–754 (1999).",{"doi":666},"10.1083\u002Fjcb.146.4.741",{"id":24,"text":668,"url":24,"identifiers":669},"Grove, S. N., Bracker, C. E. & Morré, D. J. Cytomembrane differentiation in the endoplasmic reticulum–Golgi apparatus–vesicle complex. Science 161, 171–173 (1968).",{"doi":670},"10.1126\u002Fscience.161.3837.171",{"id":24,"text":672,"url":24,"identifiers":673},"Mitra, K., Ubarretxena-Belandia, I., Taguchi, T., Warren, G. & Engelman, D. M. Modulation of the bilayer thickness of exocytic pathway membranes by membrane proteins rather than cholesterol. Proc. Natl Acad. Sci. USA 101, 4083–4088 (2004).",{"doi":674},"10.1073\u002Fpnas.0307332101",{"id":24,"text":676,"url":24,"identifiers":677},"Bretscher, M. S. & Munro, S. Cholesterol and the Golgi apparatus. Science 261, 1280–1281 (1993).",{"doi":678},"10.1126\u002Fscience.8362242",{"id":24,"text":680,"url":24,"identifiers":681},"Munro, S. An investigation of the role of transmembrane domains in Golgi protein retention. EMBO J. 14, 4695–4704 (1995).",{"doi":682},"10.1002\u002Fj.1460-2075.1995.tb00151.x",{"id":24,"text":684,"url":24,"identifiers":685},"Cole, N. B., Ellenberg, J., Song, J., DiEuliis, D. & Lippincott-Schwartz, J. Retrograde transport of Golgi-localized proteins to the ER. J. Cell Biol. 140, 1–15 (1998).",{"doi":686},"10.1083\u002Fjcb.140.1.1",{"id":24,"text":688,"url":24,"identifiers":689},"Folsch, H., Ohno, H., Bonifacino, J. S. & Mellman, I. A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells. Cell 99, 189–198 (1999).",{"doi":690},"10.1016\u002FS0092-8674(00)81650-5",{"id":24,"text":692,"url":24,"identifiers":693},"Simons, K. & Ikonen, E. Functional rafts in cell membranes. Nature 387, 569–572 (1997).",{"doi":694},"10.1038\u002F42408",{"id":24,"text":696,"url":24,"identifiers":697},"Polishchuk, R., Di Pentima, A. & Lippincott-Schwartz, J. Delivery of raft-associated, GPI-anchored proteins to the apical surface of polarized MDCK cells by a transcytotic pathway. Nature Cell Biol. 6, 297–307 (2004). This live-cell-imaging study indicates that the primary site for the apical sorting of lipid-microdomain-associated GPI-anchored proteins is the basolateral plasma membrane rather than the trans -Golgi network.",{"doi":698},"10.1038\u002Fncb1109",{"id":24,"text":700,"url":24,"identifiers":701},"Parton, R. G. Caveolae — from ultrastructure to molecular mechanisms. Nature Rev. Mol. Cell Biol. 4, 162–167 (2003).",{"doi":702},"10.1038\u002Fnrm1017",{"id":24,"text":704,"url":24,"identifiers":705},"Singh, R. D. et al. Selective caveolin-1-dependent endocytosis of glycosphingolipids. Mol. Biol. Cell 14, 3254–3265 (2003).",{"doi":706},"10.1091\u002Fmbc.e02-12-0809",{"id":24,"text":708,"url":24,"identifiers":709},"Menon, A. K., Watkins, W. E. & Hrafnsdottir, S. Specific proteins are required to translocate phosphatidylcholine bidirectionally across the endoplasmic reticulum. Curr. Biol. 10, 241–252 (2000).",{"doi":710},"10.1016\u002FS0960-9822(00)00356-0",{"id":24,"text":712,"url":24,"identifiers":713},"Kol, M. A. et al. Phospholipid flop induced by transmembrane peptides in model membranes is modulated by lipid composition. Biochemistry 42, 231–327 (2003).",{"doi":714},"10.1021\u002Fbi0268403",{"id":24,"text":716,"url":24,"identifiers":717},"Helenius, J. et al. Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 protein. Nature 415, 447–450 (2002).",{"doi":718},"10.1038\u002F415447a",{"id":24,"text":720,"url":24,"identifiers":721},"Zhou, Q. et al. Molecular cloning of human plasma membrane phospholipid scramblase. A protein mediating transbilayer movement of plasma membrane phospholipids. J. Biol. Chem. 272, 18240–18244 (1997).",{"doi":722},"10.1074\u002Fjbc.272.29.18240",{"id":24,"text":724,"url":24,"identifiers":725},"Zhou, Q., Zhao, J., Wiedmer, T. & Sims, P. J. Normal hemostasis but defective hematopoietic response to growth factors in mice deficient in phospholipid scramblase 1. Blood 99, 4030–4038 (2002).",{"doi":726},"10.1182\u002Fblood-2001-12-0271",{"id":24,"text":728,"url":24,"identifiers":729},"Hirsch, D., Stahl, A. & Lodish, H. F. A family of fatty acid transporters conserved from mycobacterium to man. Proc. Natl Acad. Sci. USA 95, 8625–8629 (1998).",{"doi":730},"10.1073\u002Fpnas.95.15.8625",{"id":24,"text":732,"url":24,"identifiers":733},"Pomorski, T., Holthuis, J. C., Herrmann, A. & van Meer, G. Tracking down lipid flippases and their biological functions. J. Cell Sci. 117, 805–813 (2004).",{"doi":734},"10.1242\u002Fjcs.01055",{"id":24,"text":736,"url":24,"identifiers":737},"Natarajan, P., Wang, J., Hua, Z. & Graham, T. R. Drs2p-coupled aminophospholipid translocase activity in yeast Golgi membranes and relationship to in vivo function. Proc. Natl Acad. Sci. USA 101, 10614–10619 (2004).",{"doi":738},"10.1073\u002Fpnas.0404146101",{"id":24,"text":740,"url":24,"identifiers":741},"Pomorski, T. et al. Drs2p-related P-type ATPases Dnf1p and Dnf2p are required for phospholipid translocation across the yeast plasma membrane and serve a role in endocytosis. Mol. Biol. Cell 14, 1240–1254 (2003). Provides evidence for a functional link between P-type-ATPase-dependent lipid transport and endocytic-vesicle formation.",{"doi":742},"10.1091\u002Fmbc.e02-08-0501",{"id":24,"text":744,"url":24,"identifiers":745},"Tang, X., Halleck, M. S., Schlegel, R. A. & Williamson, P. A subfamily of P-type ATPases with aminophospholipid transporting activity. Science 272, 1495–1497 (1996). Using peptide sequences from a purified, bovine chromaffin-granule aminophospholipid-translocase activity, the authors discover a new subfamily of P-type ATPases that have a crucial function in aminophospholipid transport.",{"doi":746},"10.1126\u002Fscience.272.5267.1495",{"id":24,"text":748,"url":24,"identifiers":749},"Gomes, E., Jakobsen, M. K., Axelsen, K. B., Geisler, M. & Palmgren, M. G. Chilling tolerance in Arabidopsis involves ALA1, a member of a new family of putative aminophospholipid translocases. Plant Cell 12, 2441–2454 (2000).",{"doi":750},"10.1105\u002Ftpc.12.12.2441",{"id":24,"text":752,"url":24,"identifiers":753},"Bull, L. N. et al. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nature Genet. 18, 219–224 (1998).",{"doi":754},"10.1038\u002Fng0398-219",{"id":24,"text":756,"url":24,"identifiers":757},"Meguro, M. et al. A novel maternally expressed gene, ATP10C, encodes a putative aminophospholipid translocase associated with Angelman syndrome. Nature Genet. 28, 19–20 (2001).",{},{"id":24,"text":759,"url":24,"identifiers":760},"Chen, C. Y., Ingram, M. F., Rosal, P. H. & Graham, T. R. Role for Drs2p, a P-type ATPase and potential aminophospholipid translocase, in yeast late Golgi function. J. Cell Biol. 147, 1223–1236 (1999).",{"doi":761},"10.1083\u002Fjcb.147.6.1223",{"id":24,"text":763,"url":24,"identifiers":764},"Hua, Z., Fatheddin, P. & Graham, T. R. An essential subfamily of Drs2p-related P-type ATPases is required for protein trafficking between Golgi complex and endosomal\u002Fvacuolar system. Mol. Biol. Cell 13, 3162–3177 (2002).",{"doi":765},"10.1091\u002Fmbc.e02-03-0172",{"id":24,"text":767,"url":24,"identifiers":768},"Devaux, P. F. Is lipid translocation involved during endo- and exocytosis? Biochimie 82, 497–509 (2000). Insightful review on the physical constraints of membrane folding and the putative role of lipid translocases in vesicle formation.",{"doi":769},"10.1016\u002FS0300-9084(00)00209-1",{"id":24,"text":771,"url":24,"identifiers":772},"Muller, P., Pomorski, T. & Herrmann, A. Incorporation of phospholipid analogues into the plasma membrane affects ATP-induced vesiculation of human erythrocyte ghosts. Biochem. Biophys. Res. Commun. 199, 881–887 (1994).",{"doi":773},"10.1006\u002Fbbrc.1994.1311",{"id":24,"text":775,"url":24,"identifiers":776},"Saito, K. et al. Cdc50p, a protein required for polarized growth, associates with the Drs2p P-type ATPase implicated in phospholipid translocation in Saccharomyces cerevisiae. Mol. Biol. Cell 15, 3418–3432 (2004).",{"doi":777},"10.1091\u002Fmbc.e03-11-0829",{"id":24,"text":779,"url":24,"identifiers":780},"Weng, J. et al. Insights into the function of Rim protein in photoreceptors and etiology of Stargardt's disease from the phenotype in abcr knockout mice. Cell 98, 13–23 (1999).",{"doi":781},"10.1016\u002FS0092-8674(00)80602-9",{"id":24,"text":783,"url":24,"identifiers":784},"Smit, J. J. M. et al. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 75, 451–462 (1993).",{"doi":785},"10.1016\u002F0092-8674(93)90380-9",{"id":24,"text":787,"url":24,"identifiers":788},"van Helvoort, A. et al. MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell 87, 507–517 (1996).",{"doi":789},"10.1016\u002FS0092-8674(00)81370-7",{"id":24,"text":791,"url":24,"identifiers":792},"Decottignies, A. et al. ATPase and multidrug transport activities of the overexpressed yeast ABC protein Yor1p. J. Biol. Chem. 273, 12612–12622 (1998).",{"doi":793},"10.1074\u002Fjbc.273.20.12612",{"id":24,"text":795,"url":24,"identifiers":796},"Hamon, Y. et al. ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nature Cell Biol. 2, 399–406 (2000).",{"doi":797},"10.1038\u002F35017029",{"id":24,"text":799,"url":24,"identifiers":800},"Berge, K. E. et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290, 1771–1775 (2000).",{"doi":801},"10.1126\u002Fscience.290.5497.1771",{"id":24,"text":803,"url":24,"identifiers":804},"Hettema, E. H. et al. The ABC transporter proteins Pat1 and Pat2 are required for import of long-chain fatty acids into peroxisomes of Saccharomyces cerevisiae. EMBO J. 15, 3813–3822 (1996).",{"doi":805},"10.1002\u002Fj.1460-2075.1996.tb00755.x",{"id":24,"text":807,"url":24,"identifiers":808},"Kihara, A. & Igarashi, Y. Identification and characterization of a Saccharomyces cerevisiae gene, RSB1, involved in sphingoid long-chain base release. J. Biol. Chem. 277, 30048–30054 (2002).",{"doi":809},"10.1074\u002Fjbc.M203385200",{"id":24,"text":811,"url":24,"identifiers":812},"Wirtz, K. W. Phospholipid transfer proteins. Annu. Rev. Biochem. 60, 73–99 (1991).",{"doi":813},"10.1146\u002Fannurev.bi.60.070191.000445",{"id":24,"text":815,"url":24,"identifiers":816},"Schouten, A. et al. Structure of apo-phosphatidylinositol transfer protein α provides insight into membrane association. EMBO J. 21, 2117–2121 (2002).",{"doi":817},"10.1093\u002Femboj\u002F21.9.2117",{"id":24,"text":819,"url":24,"identifiers":820},"Sha, B., Phillips, S. E., Bankaitis, V. A. & Luo, M. Crystal structure of the Saccharomyces cerevisiae phosphatidylinositol-transfer protein. Nature 391, 506–510 (1998).",{"doi":821},"10.1038\u002F35179",{"id":24,"text":823,"url":24,"identifiers":824},"Tsujishita, Y. & Hurley, J. H. Structure and lipid transport mechanism of a StAR-related domain. Nature Struct. Biol. 7, 408–414 (2000).",{"doi":825},"10.1038\u002F75192",{"id":24,"text":827,"url":24,"identifiers":828},"Schrick, K., Nguyen, D., Karlowski, W. M. & Mayer, K. F. START lipid\u002Fsterol-binding domains are amplified in plants and are predominantly associated with homeodomain transcription factors. Genome Biol. 5, R41 (2004).",{"doi":829},"10.1186\u002Fgb-2004-5-6-r41",{"id":24,"text":831,"url":24,"identifiers":832},"Debant, A. et al. The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains. Proc. Natl Acad. Sci. USA 93, 5466–5471 (1996).",{"doi":833},"10.1073\u002Fpnas.93.11.5466",{"id":24,"text":835,"url":24,"identifiers":836},"Munro, S. Organelle identity and the targeting of peripheral membrane proteins. Curr. Opin. Cell Biol. 14, 506–514 (2002).",{"doi":837},"10.1016\u002FS0955-0674(02)00350-2",{"id":24,"text":839,"url":24,"identifiers":840},"Staehelin, L. A. The plant ER: a dynamic organelle composed of a large number of discrete functional domains. Plant J. 11, 1151–1165 (1997).",{"doi":841},"10.1046\u002Fj.1365-313X.1997.11061151.x",{"id":24,"text":843,"url":24,"identifiers":844},"Pichler, H. et al. A subfraction of the yeast endoplasmic reticulum associates with the plasma membrane and has a high capacity to synthesize lipids. Eur. J. Biochem. 268, 2351–2361 (2001).",{"doi":845},"10.1046\u002Fj.1432-1327.2001.02116.x",{"id":24,"text":847,"url":24,"identifiers":848},"Mogelsvang, S., Marsh, B. J., Ladinsky, M. S. & Howell, K. E. Predicting function from structure: 3D structure studies of the mammalian Golgi complex. Traffic 5, 338–345 (2004).",{"doi":849},"10.1111\u002Fj.1398-9219.2004.00186.x",{"id":24,"text":851,"url":24,"identifiers":852},"Haj, F. G., Verveer, P. J., Squire, A., Neel, B. G. & Bastiaens, P. I. Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum. Science 295, 1708–1711 (2002). Confirms the functional importance of ER–endosome contacts in mammalian cells, by showing that endocytosed epidermal growth factor receptor is dephosphorylated by a phosphatase that is embedded in the ER.",{"doi":853},"10.1126\u002Fscience.1067566",{"id":24,"text":855,"url":24,"identifiers":856},"Pan, X. et al. Nucleus–vacuole junctions in Saccharomyces cerevisiae are formed through the direct interaction of Vac8p with Nvj1p. Mol. Biol. Cell 11, 2445–2457 (2000).",{"doi":857},"10.1091\u002Fmbc.11.7.2445",{"id":24,"text":859,"url":24,"identifiers":860},"Sinai, A. P. & Joiner, K. A. The Toxoplasma gondii protein ROP2 mediates host organelle association with the parasitophorous vacuole membrane. J. Cell Biol. 154, 95–108 (2001).",{"doi":861},"10.1083\u002Fjcb.200101073",{"id":24,"text":863,"url":24,"identifiers":864},"Achleitner, G. et al. Association between the endoplasmic reticulum and mitochondria of yeast facilitates interorganelle transport of phospholipids through membrane contact. Eur. J. Biochem. 264, 545–553 (1999).",{"doi":865},"10.1046\u002Fj.1432-1327.1999.00658.x",{"id":24,"text":867,"url":24,"identifiers":868},"Xu, C., Fan, J., Riekhof, W., Froehlich, J. E. & Benning, C. A permease-like protein involved in ER to thylakoid lipid transfer in Arabidopsis. EMBO J. 22, 2370–2379 (2003).",{"doi":869},"10.1093\u002Femboj\u002Fcdg234",{"id":24,"text":871,"url":24,"identifiers":872},"Milla, P. et al. Yeast oxidosqualene cyclase (Erg7p) is a major component of lipid particles. J. Biol. Chem. 277, 2406–2412 (2002).",{"doi":873},"10.1074\u002Fjbc.M104195200",{"id":24,"text":875,"url":24,"identifiers":876},"Underwood, K. W., Jacobs, N. L., Howley, A. & Liscum, L. Evidence for a cholesterol transport pathway from lysosomes to endoplasmic reticulum that is independent of the plasma membrane. J. Biol. Chem. 273, 4266–4274 (1998).",{"doi":877},"10.1074\u002Fjbc.273.7.4266",{"id":24,"text":879,"url":24,"identifiers":880},"Coppens, I., Sinai, A. P. & Joiner, K. A. Toxoplasma gondii exploits host low-density lipoprotein receptor-mediated endocytosis for cholesterol acquisition. J. Cell Biol. 149, 167–180 (2000).",{"doi":881},"10.1083\u002Fjcb.149.1.167",{"id":24,"text":883,"url":24,"identifiers":884},"Shiao, Y. J., Balcerzak, B. & Vance, J. E. A mitochondrial membrane protein is required for translocation of phosphatidylserine from mitochondria-associated membranes to mitochondria. Biochem. J. 331, 217–223 (1998).",{"doi":885},"10.1042\u002Fbj3310217",{"id":24,"text":887,"url":24,"identifiers":888},"Severs, N. J., Jordan, E. G. & Williamson, D. H. Nuclear pore absence from areas of close association between nucleus and vacuole in synchronous yeast cultures. J. Ultrastruct. Res. 54, 374–387 (1976).",{"doi":889},"10.1016\u002FS0022-5320(76)80023-8",{"id":24,"text":891,"url":24,"identifiers":892},"Rizzuto, R., Duchen, M. R. & Pozzan, T. Flirting in little space: the ER\u002Fmitochondria Ca2+ liaison. Sci. STKE 2004, re1 (2004).",{"doi":893},"10.1126\u002Fstke.2152004re1",{"id":24,"text":895,"url":24,"identifiers":896},"Loewen, C. J., Roy, A. & Levine, T. P. A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP. EMBO J. 22, 2025–2035 (2003). Identifies a conserved interaction between various LTPs and the ER, and shows that this targeting can be integrated with PH-domain interactions to target MCSs.",{"doi":897},"10.1093\u002Femboj\u002Fcdg201",{"id":24,"text":899,"url":24,"identifiers":900},"Vihtelic, T. S., Goebl, M., Milligan, S., O'Tousa, J. E. & Hyde, D. R. Localization of Drosophila retinal degeneration B, a membrane-associated phosphatidylinositol transfer protein. J. Cell Biol. 122, 1013–1022 (1993).",{"doi":901},"10.1083\u002Fjcb.122.5.1013",{"id":24,"text":903,"url":24,"identifiers":904},"Milligan, S. C., Alb, J. G. Jr, Elagina, R. B., Bankaitis, V. A. & Hyde, D. R. The phosphatidylinositol transfer protein domain of Drosophila retinal degeneration B protein is essential for photoreceptor cell survival and recovery from light stimulation. J. Cell Biol. 139, 351–363 (1997).",{"doi":905},"10.1083\u002Fjcb.139.2.351",{"id":24,"text":907,"url":24,"identifiers":908},"Wu, W. I. & Voelker, D. R. Reconstitution of phosphatidylserine transport from chemically defined donor membranes to phosphatidylserine decarboxylase 2 implicates specific lipid domains in the process. J. Biol. Chem. 279, 6635–6642 (2004). Discusses a functional analysis of gene products that were previously identified to have a role in the non-vesicular transport of phosphatidylserine, and describes the precise biochemical requirements for lipid extraction from donor membranes.",{"doi":909},"10.1074\u002Fjbc.M311570200",{"id":24,"text":911,"url":24,"identifiers":912},"Levine, T. P. & Munro, S. Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4-kinase-dependent and-independent components. Curr. Biol. 12, 695–704 (2002).",{"doi":913},"10.1016\u002FS0960-9822(02)00779-0",{"id":24,"text":915,"url":24,"identifiers":916},"Novikoff, A. B. GERL, its form and function in neurons of rat spinal ganglia. Biol. Bull. 127, 358 (1964).",{},{"id":24,"text":918,"url":24,"identifiers":919},"Ridgway, N. D., Dawson, P. A., Ho, Y. K., Brown, M. S. & Goldstein, J. L. Translocation of oxysterol binding protein to Golgi apparatus triggered by ligand binding. J. Cell Biol. 116, 307–319 (1992).",{"doi":920},"10.1083\u002Fjcb.116.2.307",{"id":24,"text":922,"url":24,"identifiers":923},"Alpy, F. et al. The steroidogenic acute regulatory protein homolog MLN64, a late endosomal cholesterol-binding protein. J. Biol. Chem. 276, 4261–4269 (2001).",{"doi":924},"10.1074\u002Fjbc.M006279200",{"id":24,"text":926,"url":24,"identifiers":927},"Cunningham, E. et al. The yeast and mammalian isoforms of phosphatidylinositol transfer protein can all restore phospholipase C-mediated inositol lipid signaling in cytosol-depleted RBL-2H3 and HL-60 cells. Proc. Natl Acad. Sci. USA 93, 6589–6593 (1996).",{"doi":928},"10.1073\u002Fpnas.93.13.6589",{"id":24,"text":930,"url":24,"identifiers":931},"Fleischer, B., Zambrano, F. & Fleischer, S. Biochemical characterization of the Golgi complex of mammalian cells. J. Supramol. Struct. 2, 737–750 (1974).",{"doi":932},"10.1002\u002Fjss.400020517",{"id":24,"text":934,"url":24,"identifiers":935},"Keenan, T. W. & Morre, D. J. Phospholipid class and fatty acid composition of Golgi apparatus isolated from rat liver and comparison with other cell fractions. Biochemistry 9, 19–25 (1970).",{"doi":936},"10.1021\u002Fbi00803a003",{"id":24,"text":938,"url":24,"identifiers":939},"Zachowski, A. Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochem. J. 294, 1–14 (1993).",{"doi":940},"10.1042\u002Fbj2940001",{"id":24,"text":942,"url":24,"identifiers":943},"Leventis, R. & Silvius, J. R. Use of cyclodextrins to monitor transbilayer movement and differential lipid affinities of cholesterol. Biophys. J. 81, 2257–2267 (2001).",{"doi":944},"10.1016\u002FS0006-3495(01)75873-0",{"id":24,"text":946,"url":24,"identifiers":947},"Holthuis, J. C., van Meer, G. & Huitema, K. Lipid microdomains, lipid translocation and the organization of intracellular membrane transport. Mol. Membr. Biol. 20, 231–241 (2003).",{"doi":948},"10.1080\u002F0988768031000100768",{"id":24,"text":950,"url":24,"identifiers":951},"Levine, T. P. Short-range intracellular traffic of small molecules via endoplasmic reticulum junctions. Trends Cell Biol. 9, 483–490 (2004).",{"doi":952},"10.1016\u002Fj.tcb.2004.07.017",{"id":954,"createTime":955,"updateTime":956,"relativeEntities":957,"slug":958,"properties":959,"entityType":131,"verifyStatus":132,"verifyTime":955,"verifyNote":133,"languages":973,"translateLanguages":24,"viewCount":25,"primaryUrl":974,"fullTextUrl":24,"authors":975,"publicationType":174,"publisherRelationship":1052,"citationCount":1107,"citationInfo":1108,"publishDate":1120,"publishYear":1109,"citationAnalyzeStatus":247,"lastCitationAnalyze":1121,"indexDatabases":1122,"openAccess":24,"references":1123,"isForceReanalyzing":409},"d2e187eb-ff7d-4d2e-8127-0ba07c0eec30","2024-09-22T18:44:07.356+00:00","2026-06-16T07:41:37.973+00:00",[],"Forcing-cells-into-shape-the-mechanics-of-actomyosin-contractility",{"mag":960,"gsPaper":962,"pmc":963,"openalex":965,"title":967,"pm":969,"doi":971},{"VOID":961},"1587940648",{"VOID":126},{"VOID":964},"7443980",{"VOID":966},"W1587940648",{"EN":968},"Forcing cells into shape: the mechanics of actomyosin contractility",{"VOID":970},"26130009",{"VOID":972},"10.1038\u002Fnrm4012",[135],"https:\u002F\u002Fwww.nature.com\u002Farticles\u002Fnrm4012",[976,995,1014,1034],{"id":977,"sortIndex":25,"researcher":24,"roles":978,"affiliations":979,"properties":988,"displayName":992,"givenName":24,"familyName":24},"bd73b4bb-4f54-4a0c-a86a-6f59aaa886be",[],[980],{"id":981,"sortIndex":25,"affiliation":982,"properties":24},"a5f7518e-3070-4319-9930-ba49c82176bf",{"id":981,"createTime":24,"updateTime":24,"relativeEntities":983,"slug":24,"properties":984,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":987,"statistic":24},[],{"title":985},{"EN":986},"Department of Biomedical Engineering, Yale University, New Haven, 06520, Connecticut, USA",[],{"orcid":989,"title":991,"openalex":993},{"VOID":990},"https:\u002F\u002Forcid.org\u002F0000-0001-6788-2077",{"EN":992},"Michael P. Murrell",{"VOID":994},"A5055359361",{"id":996,"sortIndex":99,"researcher":24,"roles":997,"affiliations":998,"properties":1007,"displayName":1011,"givenName":24,"familyName":24},"1cd17022-ceb8-4de2-bb5b-319e690c8db6",[],[999],{"id":1000,"sortIndex":25,"affiliation":1001,"properties":24},"5325b830-ed42-4334-847b-0bf33503f702",{"id":1000,"createTime":24,"updateTime":24,"relativeEntities":1002,"slug":24,"properties":1003,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":1006,"statistic":24},[],{"title":1004},{"EN":1005},"Department of Physics, Institute for Biophysical Dynamics and James Franck Institute, University of Chicago, Chicago, 60637, Illinois, USA",[],{"orcid":1008,"title":1010,"openalex":1012},{"VOID":1009},"https:\u002F\u002Forcid.org\u002F0000-0001-9951-1318",{"EN":1011},"Patrick W. Oakes",{"VOID":1013},"A5004278648",{"id":1015,"sortIndex":1016,"researcher":24,"roles":1017,"affiliations":1018,"properties":1027,"displayName":1031,"givenName":24,"familyName":24},"c75098d5-77f0-436c-bcc1-9d70a93bc6b4",2,[],[1019],{"id":1020,"sortIndex":25,"affiliation":1021,"properties":24},"6c553561-764e-4b3b-aaaa-66844dd6561c",{"id":1020,"createTime":24,"updateTime":24,"relativeEntities":1022,"slug":24,"properties":1023,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":1026,"statistic":24},[],{"title":1024},{"EN":1025},"Université Paris-Sud, CNRS, LPTMS, UMR 8626, Orsay, 91405, France",[],{"orcid":1028,"title":1030,"openalex":1032},{"VOID":1029},"https:\u002F\u002Forcid.org\u002F0000-0002-2307-1106",{"EN":1031},"Martin Lenz",{"VOID":1033},"A5072398869",{"id":1035,"sortIndex":1036,"researcher":24,"roles":1037,"affiliations":1038,"properties":1045,"displayName":1049,"givenName":24,"familyName":24},"dbb1613b-236a-4bfd-b1e7-5949104ec612",3,[],[1039],{"id":1000,"sortIndex":25,"affiliation":1040,"properties":24},{"id":1000,"createTime":24,"updateTime":24,"relativeEntities":1041,"slug":24,"properties":1042,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":1044,"statistic":24},[],{"title":1043},{"EN":1005},[],{"orcid":1046,"title":1048,"openalex":1050},{"VOID":1047},"https:\u002F\u002Forcid.org\u002F0000-0003-1846-9854",{"EN":1049},"Margaret L. Gardel",{"VOID":1051},"A5005425034",{"url":24,"publisher":1053,"properties":1100},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1054,"slug":10,"properties":1055,"entityType":22,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":25,"subjectFields":1060,"manageAffiliations":1069,"indexDatabases":1080,"url":90,"thumbnailPath":24,"statistic":1095,"gsStatistic":24,"type":24,"analyzePriority":24},[],{"country":1056,"eissn":1057,"issn":1058,"title":1059},{"VOID":13},{"VOID":15},{"VOID":17},{"EN":19},[1061,1065],{"id":28,"createTime":24,"updateTime":24,"relativeEntities":1062,"label":1063,"description":1064,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":31},{},{"id":34,"createTime":24,"updateTime":24,"relativeEntities":1066,"label":1067,"description":1068,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":37},{},[1070,1075],{"id":41,"createTime":24,"updateTime":24,"relativeEntities":1071,"slug":24,"properties":1072,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":1074,"statistic":24},[],{"title":1073},{"EN":45},[],{"id":48,"createTime":24,"updateTime":24,"relativeEntities":1076,"slug":24,"properties":1077,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":1079,"statistic":24},[],{"title":1078},{"EN":52},[],[1081,1088],{"id":56,"indexDatabase":1082,"url":69,"indexYears":24,"academicFieldIds":1087,"indexDatabaseRanking":24},{"id":58,"createTime":24,"updateTime":24,"relativeEntities":1083,"label":1084,"description":1085,"key":65,"publicationTags":1086,"standard":24},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":1089,"url":84,"indexYears":85,"academicFieldIds":1094,"indexDatabaseRanking":89},{"id":75,"createTime":24,"updateTime":24,"relativeEntities":1090,"label":1091,"description":1092,"key":81,"publicationTags":1093,"standard":24},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88],{"impactFactor":25,"impactFactorByYear":1096,"i10Index":97,"i10IndexLast5Year":25,"totalPublication":97,"totalPublicationByYear":1097,"totalCitation":100,"totalCitationByYear":1098,"totalCitationPerPublication":106,"totalCitationPerPublicationByYear":1099,"hindexLast5Year":97,"hindex":97},{"2016":93,"2017":94,"2019":95,"2020":96},{"2007":99,"2009":99,"2015":99,"2018":99},{"2007":102,"2009":103,"2015":104,"2018":105},{"2007":102,"2009":103,"2015":104,"2018":105},{"issue":1101,"pages":1103,"volume":1105},{"VOID":1102},"8",{"VOID":1104},"486-498",{"VOID":1106},"16",547,{"total":1107,"publishYear":1109,"statisticByYear":1110},2015,{"2015":1036,"2016":1111,"2017":1112,"2018":1113,"2019":1114,"2020":1115,"2021":1116,"2022":1117,"2023":1118,"2024":1119},31,49,73,52,68,81,64,55,66,"2015-08-01","2026-06-16T07:41:37.972+00:00",[67,89],[1124,1128,1132,1136,1140,1144,1148,1152,1156,1160,1164,1168,1172,1176,1180,1184,1188,1192,1196,1200,1204,1208,1212,1216,1220,1224,1228,1232,1236,1240,1244,1248,1252,1256,1260,1264,1268,1272,1276,1280,1284,1288,1292,1296,1300,1304,1308,1312,1316,1320,1324,1328,1332,1336,1340,1344,1347,1351,1355,1359,1363,1367,1371,1375,1379,1383,1387,1391,1395,1399,1403,1407,1411,1415,1419,1423,1427,1431,1435,1439,1443,1447,1451,1455,1459,1463,1467,1471,1475,1479,1483,1487,1491,1495,1499,1503,1507,1511,1515,1519,1523,1527,1531,1535,1539,1543,1547,1550,1554,1558,1562,1566,1570,1574,1578,1582,1586,1590,1594,1598,1602,1606,1610,1614,1618,1622,1626,1630,1634,1638,1642,1646,1650,1654,1658],{"id":24,"text":1125,"url":24,"identifiers":1126},"Munjal, A. & Lecuit, T. Actomyosin networks and tissue morphogenesis. Development 141, 1789–1793 (2014).",{"doi":1127},"10.1242\u002Fdev.091645",{"id":24,"text":1129,"url":24,"identifiers":1130},"Gardel, M. L., Schneider, I. C., Aratyn-Schaus, Y. & Waterman, C. M. Mechanical integration of actin and adhesion dynamics in cell migration. Annu. Rev. Cell Dev. Biol. 26, 315–333 (2010).",{"doi":1131},"10.1146\u002Fannurev.cellbio.011209.122036",{"id":24,"text":1133,"url":24,"identifiers":1134},"Vicente-Manzanares, M., Ma, X., Adelstein, R. S. & Horwitz, A. R. Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat. Rev. Mol. Cell Biol. 10, 778–790 (2009).",{"doi":1135},"10.1038\u002Fnrm2786",{"id":24,"text":1137,"url":24,"identifiers":1138},"Salbreux, G., Charras, G. & Paluch, E. Actin cortex mechanics and cellular morphogenesis. Trends Cell Biol. 10, 536–545 (2012).",{"doi":1139},"10.1016\u002Fj.tcb.2012.07.001",{"id":24,"text":1141,"url":24,"identifiers":1142},"Green, R. A., Paluch, E. & Oegema, K. Cytokinesis in animal cells. Annu. Rev. Cell Dev. Biol. 28, 29–58 (2012).",{"doi":1143},"10.1146\u002Fannurev-cellbio-101011-155718",{"id":24,"text":1145,"url":24,"identifiers":1146},"Pinto, I. M. et al. Actin depolymerization drives actomyosin ring contraction during budding yeast cytokinesis. Dev. Cell 22, 1247–1260 (2012).",{"doi":1147},"10.1016\u002Fj.devcel.2012.04.015",{"id":24,"text":1149,"url":24,"identifiers":1150},"Murrell, M. P. et al. Liposome adhesion generates traction stress. Nat. Phys. 10, 163–169 (2014).",{"doi":1151},"10.1038\u002Fnphys2855",{"id":24,"text":1153,"url":24,"identifiers":1154},"Stroka, K. M. et al. Water permeation drives tumor cell migration in confined microenvironments. Cell 157, 611–623 (2014).",{"doi":1155},"10.1016\u002Fj.cell.2014.02.052",{"id":24,"text":1157,"url":24,"identifiers":1158},"Levayer, R. & Lecuit, T. Biomechanical regulation of contractility: spatial control and dynamics. Trends Cell Biol. 22, 61–81 (2012).",{"doi":1159},"10.1016\u002Fj.tcb.2011.10.001",{"id":24,"text":1161,"url":24,"identifiers":1162},"Lecuit, T., Lenne, P.-F. & Munro, E. Force generation, transmission, and integration during cell and tissue morphogenesis. Ann. Rev. Cell Dev. Bio 27, 157–184 (2011).",{"doi":1163},"10.1146\u002Fannurev-cellbio-100109-104027",{"id":24,"text":1165,"url":24,"identifiers":1166},"Gordon, A. M., Homsher, E. & Regnier, M. Regulation of contraction in striated muscle. Physiol. Rev. 80, 853–924 (2000).",{"doi":1167},"10.1152\u002Fphysrev.2000.80.2.853",{"id":24,"text":1169,"url":24,"identifiers":1170},"Huxley, H. E. Fifty years of muscle and the sliding filament hypothesis. Eur. J. Biochem. 271, 1403–1415 (2004).",{"doi":1171},"10.1111\u002Fj.1432-1033.2004.04044.x",{"id":24,"text":1173,"url":24,"identifiers":1174},"Steinmetz, P. R. H. et al. Independent evolution of striated muscles in cnidarians and bilaterians. Nature 487, 231–234 (2012).",{"doi":1175},"10.1038\u002Fnature11180",{"id":24,"text":1177,"url":24,"identifiers":1178},"Niederman, R. & Pollard, T. D. Human platelet myosin. II. In vitro assembly and structure of myosin filaments. J. Cell Biol. 67, 72–92 (1975).",{"doi":1179},"10.1083\u002Fjcb.67.1.72",{"id":24,"text":1181,"url":24,"identifiers":1182},"Pollard, T. D. Structure and polymerization of Acanthamoeba myosin-II filaments. J. Cell Biol. 95, 816–825 (1982).",{"doi":1183},"10.1083\u002Fjcb.95.3.816",{"id":24,"text":1185,"url":24,"identifiers":1186},"Skubiszak, L. & Kowalczyk, L. Myosin molecule packing within the vertebrate skeletal muscle thick filaments. A complete bipolar model. Acta Biochim. Polon. 49, 829–840 (2002).",{"doi":1187},"10.18388\u002Fabp.2002_3743",{"id":24,"text":1189,"url":24,"identifiers":1190},"Sobieszek, A. Cross-bridges on self-assembled smooth muscle myosin filaments. J. Mol. Biol. 70, 741–744 (1972).",{"doi":1191},"10.1016\u002F0022-2836(72)90573-6",{"id":24,"text":1193,"url":24,"identifiers":1194},"Tonino, P., Simon, M. & Craig, R. Mass determination of native smooth muscle myosin filaments by scanning transmission electron microscopy. J. Mol. Biol. 318, 999–1007 (2002).",{"doi":1195},"10.1016\u002FS0022-2836(02)00191-2",{"id":24,"text":1197,"url":24,"identifiers":1198},"Huxley, H. E. X-ray analysis and the problem of muscle. Proc. R. Soc. Lond. B 141, 59–62 (1953).",{"doi":1199},"10.1098\u002Frspb.1953.0017",{"id":24,"text":1201,"url":24,"identifiers":1202},"Huxley, H. E. The double array of filaments in cross-striated muscle. J. Biophys. Biochem. Cytol. 3, 631–648 (1957).",{"doi":1203},"10.1083\u002Fjcb.3.5.631",{"id":24,"text":1205,"url":24,"identifiers":1206},"Huxley, A. F. Muscle structure and theories of contraction. Prog. Biophys. Biophys. Chem. 7, 255–318 (1957).",{"doi":1207},"10.1016\u002FS0096-4174(18)30128-8",{"id":24,"text":1209,"url":24,"identifiers":1210},"Huxley, A. F. & Niedergerke, R. Structural changes in muscle during contraction: interference microscopy of living muscle fibres. Nature 173, 971–973 (1954).",{"doi":1211},"10.1038\u002F173971a0",{"id":24,"text":1213,"url":24,"identifiers":1214},"Littlefield, R., Almenar-Queralt, A. & Fowler, V. M. Actin dynamics at pointed ends regulates thin filament length in striated muscle. Nat. Cell Biol. 3, 544–551 (2001).",{"doi":1215},"10.1038\u002F35078517",{"id":24,"text":1217,"url":24,"identifiers":1218},"Lavoie, T. L. et al. Disrupting actin–myosin–actin connectivity in airway smooth muscle as a treatment for asthma? Proc. Am. Thorac. Soc. 6, 295–300 (2009).",{"doi":1219},"10.1513\u002Fpats.200808-078RM",{"id":24,"text":1221,"url":24,"identifiers":1222},"Gunst, S. J. & Zhang, W. Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction. Am. J. Physiol. Cell Physiol. 295, C576–587 (2008).",{"doi":1223},"10.1152\u002Fajpcell.00253.2008",{"id":24,"text":1225,"url":24,"identifiers":1226},"Verkhovsky, A. B. & Borisy, G. G. Non-sarcomeric mode of myosin II organization in the fibroblast lamellum. J. Cell Biol. 123, 637–652 (1993).",{"doi":1227},"10.1083\u002Fjcb.123.3.637",{"id":24,"text":1229,"url":24,"identifiers":1230},"Svitkina, T. M., Verkhovsky, A. B., McQuade, K. M. & Borisy, G. G. Analysis of the actin–myosin II system in fish epidermal keratocytes: mechanism of cell body translocation. J. Cell Biol. 139, 397–415 (1997).",{"doi":1231},"10.1083\u002Fjcb.139.2.397",{"id":24,"text":1233,"url":24,"identifiers":1234},"Aratyn-Schaus, Y., Oakes, P. W. & Gardel, M. L. Dynamic and structural signatures of lamellar actomyosin force generation. Mol. Biol. Cell 22, 1330–1339 (2011).",{"doi":1235},"10.1091\u002Fmbc.e10-11-0891",{"id":24,"text":1237,"url":24,"identifiers":1238},"Hotulainen, P. & Lappalainen, P. Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J. Cell Biol. 173, 383–394 (2006).",{"doi":1239},"10.1083\u002Fjcb.200511093",{"id":24,"text":1241,"url":24,"identifiers":1242},"Svitkina, T. M. & Borisy, G. G. Correlative light and electron microscopy of the cytoskeleton of cultured cells. Methods Enzymol. 298, 570–592 (1998).",{"doi":1243},"10.1016\u002FS0076-6879(98)98045-4",{"id":24,"text":1245,"url":24,"identifiers":1246},"Stricker, J., Beckham, Y., Davidson, M. W. & Gardel, M. L. Myosin II-mediated focal adhesion maturation is tension insensitive. PLoS ONE 8, e70652 (2013).",{"doi":1247},"10.1371\u002Fjournal.pone.0070652",{"id":24,"text":1249,"url":24,"identifiers":1250},"Oakes, P. W., Beckham, Y., Stricker, J. & Gardel, M. L. Tension is required but not sufficient for focal adhesion maturation without a stress fiber template. J. Cell Bio. 196, 363–374 (2012).",{"doi":1251},"10.1083\u002Fjcb.201107042",{"id":24,"text":1253,"url":24,"identifiers":1254},"Martin, A. C. et al. Integration of contractile forces during tissue invagination. J. Cell Biol. 188, 735–749 (2010).",{"doi":1255},"10.1083\u002Fjcb.200910099",{"id":24,"text":1257,"url":24,"identifiers":1258},"Martin, A. C., Kaschube, M. & Wieschaus, E. F. Pulsed contractions of an actin–myosin network drive apical constriction. Nature 457, 495–499 (2009).",{"doi":1259},"10.1038\u002Fnature07522",{"id":24,"text":1261,"url":24,"identifiers":1262},"He, L., Wang, X., Tang, H. L. & Montell, D. J. Tissue elongation requires oscillating contractions of a basal actomyosin network. Nat. Cell Biol. 12, 1133–1142 (2010).",{"doi":1263},"10.1038\u002Fncb2124",{"id":24,"text":1265,"url":24,"identifiers":1266},"Levayer, R. & Lecuit, T. Oscillation and polarity of E-cadherin asymmetries control actomyosin flow patterns during morphogenesis. Dev. Cell 26, 162–175 (2013).",{"doi":1267},"10.1016\u002Fj.devcel.2013.06.020",{"id":24,"text":1269,"url":24,"identifiers":1270},"Kim, T., Gardel, M. L. & Munro, E. Determinants of fluidlike behavior and effective viscosity in cross-linked actin networks. Biophys. J. 106, 526–534 (2014).",{"doi":1271},"10.1016\u002Fj.bpj.2013.12.031",{"id":24,"text":1273,"url":24,"identifiers":1274},"Courtemanche, N., Lee, J. Y., Pollard, T. D. & Greene, E. C. Tension modulates actin filament polymerization mediated by formin and profilin. Proc. Natl Acad. Sci. USA 110, 9752–9757 (2013).",{"doi":1275},"10.1073\u002Fpnas.1308257110",{"id":24,"text":1277,"url":24,"identifiers":1278},"Ferrer, J. M. et al. Measuring molecular rupture forces between single actin filaments and actin-binding proteins. Proc. Natl Acad. Sci. USA 105, 9221–9226 (2008).",{"doi":1279},"10.1073\u002Fpnas.0706124105",{"id":24,"text":1281,"url":24,"identifiers":1282},"Jégou, A., Carlier, M.-F. & Romet-Lemonne, G. Formin mDia1 senses and generates mechanical forces on actin filaments. Nat. Commun. 4, 1883 (2013).",{"doi":1283},"10.1038\u002Fncomms2888",{"id":24,"text":1285,"url":24,"identifiers":1286},"Wilson, C. A. et al. Myosin II contributes to cell-scale actin network treadmilling through network disassembly. Nature 465, 373–377 (2010).",{"doi":1287},"10.1038\u002Fnature08994",{"id":24,"text":1289,"url":24,"identifiers":1290},"Fritzsche, M. et al. Analysis of turnover dynamics of the submembranous actin cortex. Mol. Biol. Cell 24, 757–767 (2013).",{"doi":1291},"10.1091\u002Fmbc.e12-06-0485",{"id":24,"text":1293,"url":24,"identifiers":1294},"Carvalho, A., Desai, A. & Oegema, K. Structural memory in the contractile ring makes the duration of cytokinesis independent of cell size. Cell 137, 926–937 (2009).",{"doi":1295},"10.1016\u002Fj.cell.2009.03.021",{"id":24,"text":1297,"url":24,"identifiers":1298},"Luo, W. et al. Analysis of the local organization and dynamics of cellular actin networks. J. Cell Biol. 202, 1057–1073 (2013).",{"doi":1299},"10.1083\u002Fjcb.201210123",{"id":24,"text":1301,"url":24,"identifiers":1302},"Lenz, M., Gardel, M. L. & Dinner, A. R. Requirements for contractility in disordered cytoskeletal bundles. New J. Phys. 14, 033037 (2012).",{"doi":1303},"10.1088\u002F1367-2630\u002F14\u002F3\u002F033037",{"id":24,"text":1305,"url":24,"identifiers":1306},"Vavylonis, D. et al. Assembly mechanism of the contractile ring for cytokinesis by fission yeast. Science 319, 97–100 (2008).",{"doi":1307},"10.1126\u002Fscience.1151086",{"id":24,"text":1309,"url":24,"identifiers":1310},"Kruse, K. & Julicher, F. Actively contracting bundles of polar filaments. Phys. Rev. Lett. 85, 1778–1781 (2000).",{"doi":1311},"10.1103\u002FPhysRevLett.85.1778",{"id":24,"text":1313,"url":24,"identifiers":1314},"Liverpool, T. B. & Marchetti, M. C. Bridging the microscopic and the hydrodynamic in active filament solutions. Europhys. Lett. 69, 846 (2005).",{"doi":1315},"10.1209\u002Fepl\u002Fi2004-10414-0",{"id":24,"text":1317,"url":24,"identifiers":1318},"Tsuda, Y., Yasutake, H., Ishijima, A. & Yanagida, T. Torsional rigidity of single actin filaments and actin–actin bond breaking force under torsion measured directly by in vitro micromanipulation. Proc. Natl Acad. Sci. USA 93, 12937–12942 (1996).",{"doi":1319},"10.1073\u002Fpnas.93.23.12937",{"id":24,"text":1321,"url":24,"identifiers":1322},"McCullough, B. R. et al. Cofilin-linked changes in actin filament flexibility promote severing. Biophys. J. 101, 151–159 (2011).",{"doi":1323},"10.1016\u002Fj.bpj.2011.05.049",{"id":24,"text":1325,"url":24,"identifiers":1326},"Arai, Y. et al. Tying a molecular knot with optical tweezers. Nature 399, 446–448 (1999).",{"doi":1327},"10.1038\u002F20894",{"id":24,"text":1329,"url":24,"identifiers":1330},"Lenz, M., Thoresen, T., Gardel, M. L. & Dinner, A. R. Contractile units in disordered actomyosin bundles arise from F-actin buckling. Phys. Rev. Lett. 108, 238107 (2012).",{"doi":1331},"10.1103\u002FPhysRevLett.108.238107",{"id":24,"text":1333,"url":24,"identifiers":1334},"Murrell, M. P. & Gardel, M. L. F-actin buckling coordinates contractility and severing in a biomimetic actomyosin cortex. Proc. Natl Acad. Sci. USA 51, 20820–20825 (2012).",{"doi":1335},"10.1073\u002Fpnas.1214753109",{"id":24,"text":1337,"url":24,"identifiers":1338},"Hayakawa, K., Tatsumi, H. & Sokabe, M. Actin filaments function as a tension sensor by tension-dependent binding of cofilin to the filament. J. Cell Biol. 195, 721–727 (2011).",{"doi":1339},"10.1083\u002Fjcb.201102039",{"id":24,"text":1341,"url":24,"identifiers":1342},"Vogel, S. K., Petrasek, Z., Heinemann, F. & Schwille, P. Myosin motors fragment and compact membrane-bound actin filaments. eLife 2, e00116 (2013).",{"doi":1343},"10.7554\u002FeLife.00116",{"id":24,"text":1345,"url":24,"identifiers":1346},"Lenz, M. Geometrical origins of contractility in disordered actomyosin networks. Phys. Rev. X 4, 041002 (2014).",{},{"id":24,"text":1348,"url":24,"identifiers":1349},"Thoresen, T., Lenz, M. & Gardel, M. L. Thick filament length and isoform composition determine self-organized contractile units in actomyosin bundles. Biophys. J. 104, 655–665 (2013).",{"doi":1350},"10.1016\u002Fj.bpj.2012.12.042",{"id":24,"text":1352,"url":24,"identifiers":1353},"Haviv, L., Gillo, D., Backouche, F. & Bernheim-Groswasser, A. A cytoskeletal demolition worker: myosin II acts as an actin depolymerization agent. J. Mol. Biol. 375, 325–330 (2008).",{"doi":1354},"10.1016\u002Fj.jmb.2007.09.066",{"id":24,"text":1356,"url":24,"identifiers":1357},"Pelham, R. J. & Chang, F. Actin dynamics in the contractile ring during cytokinesis in fission yeast. Nature 419, 82–86 (2002).",{"doi":1358},"10.1038\u002Fnature00999",{"id":24,"text":1360,"url":24,"identifiers":1361},"Costa, K. D., Hucker, W. J. & Yin, F. C. Buckling of actin stress fibers: a new wrinkle in the cytoskeletal tapestry. Cell. Motil. Cytoskeleton 52, 266–274 (2002).",{"doi":1362},"10.1002\u002Fcm.10056",{"id":24,"text":1364,"url":24,"identifiers":1365},"Heissler, S. M. & Manstein, D. J. Nonmuscle myosin-2: mix and match. Cell. Mol. Life Sci. 70, 1–21 (2013).",{"doi":1366},"10.1007\u002Fs00018-012-1002-9",{"id":24,"text":1368,"url":24,"identifiers":1369},"Parsons, J. T., Horwitz, A. R. & Schwartz, M. A. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat. Rev. Mol. Cell Biol. 11, 633–643 (2010).",{"doi":1370},"10.1038\u002Fnrm2957",{"id":24,"text":1372,"url":24,"identifiers":1373},"Jordan, S. N. & Canman, J. C. Rho GTPases in animal cell cytokinesis: an occupation by the one percent. Cytoskeleton 69, 919–930 (2012).",{"doi":1374},"10.1002\u002Fcm.21071",{"id":24,"text":1376,"url":24,"identifiers":1377},"Machacek, M. et al. Coordination of Rho GTPase activities during cell protrusion. Nature 461, 99–103 (2009).",{"doi":1378},"10.1038\u002Fnature08242",{"id":24,"text":1380,"url":24,"identifiers":1381},"Munro, E. & Bowerman, B. Cellular symmetry breaking during Caenorhabditis elegans development. Cold Spring Harb. Perspect. Biol. 1, a003400 (2009).",{"doi":1382},"10.1101\u002Fcshperspect.a003400",{"id":24,"text":1384,"url":24,"identifiers":1385},"Janson, L. W., Kolega, J. & Taylor, D. L. Modulation of contraction by gelation\u002Fsolation in a reconstituted motile model. J. Cell Biol. 114, 1005–1015 (1991).",{"doi":1386},"10.1083\u002Fjcb.114.5.1005",{"id":24,"text":1388,"url":24,"identifiers":1389},"Bendix, P. M. et al. A quantitative analysis of contractility in active cytoskeletal protein networks. Biophys. J. 94, 3126–3136 (2008).",{"doi":1390},"10.1529\u002Fbiophysj.107.117960",{"id":24,"text":1392,"url":24,"identifiers":1393},"Thoresen, T., Lenz, M. & Gardel, M. L. Reconstitution of contractile actomyosin bundles. Biophys. J. 100, 2698–2705 (2011).",{"doi":1394},"10.1016\u002Fj.bpj.2011.04.031",{"id":24,"text":1396,"url":24,"identifiers":1397},"Alvarado, J. et al. Molecular motors robustly drive active gels to a critically connected state. Nat. Phys. 9, 591–597 (2013).",{"doi":1398},"10.1038\u002Fnphys2715",{"id":24,"text":1400,"url":24,"identifiers":1401},"Gardel, M. L. et al. Elastic behavior of cross-linked and bundled actin networks. Science 304, 1301–1305 (2004).",{"doi":1402},"10.1126\u002Fscience.1095087",{"id":24,"text":1404,"url":24,"identifiers":1405},"Kasza, K. E. et al. Nonlinear elasticity of stiff biopolymers connected by flexible linkers. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 79, 041928 (2009).",{"doi":1406},"10.1103\u002FPhysRevE.79.041928",{"id":24,"text":1408,"url":24,"identifiers":1409},"Kohler, S., Schaller, V. & Bausch, A. R. Structure formation in active networks. Nat. Mater. 10, 462–468 (2011).",{"doi":1410},"10.1038\u002Fnmat3009",{"id":24,"text":1412,"url":24,"identifiers":1413},"Reymann, A.-C. et al. Nucleation geometry governs ordered actin networks structures. Nat. Mater. 9, 827–832 (2010).",{"doi":1414},"10.1038\u002Fnmat2855",{"id":24,"text":1416,"url":24,"identifiers":1417},"Alexandrova, A. Y. et al. Comparative dynamics of retrograde actin flow and focal adhesions: formation of nascent adhesions triggers transition from fast to slow flow. PLoS ONE 3, e3234 (2008).",{"doi":1418},"10.1371\u002Fjournal.pone.0003234",{"id":24,"text":1420,"url":24,"identifiers":1421},"Koenderink, G. H. et al. An active biopolymer network controlled by molecular motors. Proc. Natl Acad. Sci. USA 106, 15192–15197 (2009).",{"doi":1422},"10.1073\u002Fpnas.0903974106",{"id":24,"text":1424,"url":24,"identifiers":1425},"Gardel, M. L. et al. Prestressed F-actin networks cross-linked by hinged filamins replicate mechanical properties of cells. Proc. Natl Acad. Sci. USA 103, 1762–1767 (2006).",{"doi":1426},"10.1073\u002Fpnas.0504777103",{"id":24,"text":1428,"url":24,"identifiers":1429},"Smith, M. A. et al. A zyxin-mediated mechanism for actin stress fiber maintenance and repair. Dev. Cell 19, 365–376 (2010).",{"doi":1430},"10.1016\u002Fj.devcel.2010.08.008",{"id":24,"text":1432,"url":24,"identifiers":1433},"Halder, G., Dupont, S. & Piccolo, S. Transduction of mechanical and cytoskeletal cues by YAP and TAZ. Nat. Rev. Mol. Cell Biol. 13, 591–600 (2012).",{"doi":1434},"10.1038\u002Fnrm3416",{"id":24,"text":1436,"url":24,"identifiers":1437},"Cowan, C. R. & Hyman, A. A. Acto-myosin reorganization and PAR polarity in C. elegans. Development 134, 1035–1043 (2007).",{"doi":1438},"10.1242\u002Fdev.000513",{"id":24,"text":1440,"url":24,"identifiers":1441},"Liu, C. et al. Actin-mediated feedback loops in B-cell receptor signaling. Immunol. Rev. 256, 177–189 (2013).",{"doi":1442},"10.1111\u002Fimr.12113",{"id":24,"text":1444,"url":24,"identifiers":1445},"Storm, C. et al. Nonlinear elasticity in biological gels. Nature 435, 191–194 (2005).",{"doi":1446},"10.1038\u002Fnature03521",{"id":24,"text":1448,"url":24,"identifiers":1449},"Gardel, M. L. et al. Stress-dependent elasticity of composite actin networks as a model for cell behavior. Phys. Rev. Lett. 96, 088102 (2006).",{"doi":1450},"10.1103\u002FPhysRevLett.96.088102",{"id":24,"text":1452,"url":24,"identifiers":1453},"Kasza, K. E. et al. Filamin A is essential for active cell stiffening but not passive stiffening under external force. Biophys. J. 96, 4326–4335 (2009).",{"doi":1454},"10.1016\u002Fj.bpj.2009.02.035",{"id":24,"text":1456,"url":24,"identifiers":1457},"Mizuno, D., Tardin, C., Schmidt, C. F. & Mackintosh, F. C. Nonequilibrium mechanics of active cytoskeletal networks. Science 315, 370–373 (2007).",{"doi":1458},"10.1126\u002Fscience.1134404",{"id":24,"text":1460,"url":24,"identifiers":1461},"Pasternak, C., Spudich, J. A. & Elson, E. L. Capping of surface receptors and concomitant cortical tension are generated by conventional myosin. Nature 341, 549–551 (1989).",{"doi":1462},"10.1038\u002F341549a0",{"id":24,"text":1464,"url":24,"identifiers":1465},"Wang, N. et al. Cell prestress. I. Stiffness and prestress are closely associated in adherent contractile cells. Am. J. Physiol. Cell Physiol. 282, C606–616 (2002).",{"doi":1466},"10.1152\u002Fajpcell.00269.2001",{"id":24,"text":1468,"url":24,"identifiers":1469},"Stamenovic, D., Liang, Z., Chen, J. & Wang, N. Effect of the cytoskeletal prestress on the mechanical impedance of cultured airway smooth muscle cells. J. Appl. Physiol. 92, 1443–1450 (2002).",{"doi":1470},"10.1152\u002Fjapplphysiol.00782.2001",{"id":24,"text":1472,"url":24,"identifiers":1473},"Balland, M., Richert, A. & Gallet, F. The dissipative contribution of myosin II in the cytoskeleton dynamics of myoblasts. Eur. Biophys. J. 34, 255–261 (2005).",{"doi":1474},"10.1007\u002Fs00249-004-0447-7",{"id":24,"text":1476,"url":24,"identifiers":1477},"Martens, J. C. & Radmacher, M. Softening of the actin cytoskeleton by inhibition of myosin II. Pflugers Arch. 456, 95–100 (2008).",{"doi":1478},"10.1007\u002Fs00424-007-0419-8",{"id":24,"text":1480,"url":24,"identifiers":1481},"Lau, A. W. et al. Microrheology, stress fluctuations, and active behavior of living cells. Phys. Rev. Lett. 91, 198101 (2003).",{"doi":1482},"10.1103\u002FPhysRevLett.91.198101",{"id":24,"text":1484,"url":24,"identifiers":1485},"Brangwynne, C. P. et al. Microtubules can bear enhanced compressive loads in living cells because of lateral reinforcement. J. Cell Biol. 173, 733–741 (2006).",{"doi":1486},"10.1083\u002Fjcb.200601060",{"id":24,"text":1488,"url":24,"identifiers":1489},"Fakhri, N. et al. High-resolution mapping of intracellular fluctuations using carbon nanotubes. Science 344, 1031–1035 (2014).",{"doi":1490},"10.1126\u002Fscience.1250170",{"id":24,"text":1492,"url":24,"identifiers":1493},"Manneville, J. B., Bassereau, P., Levy, D. & Prost, J. Activity of transmembrane proteins induces magnification of shape fluctuations of lipid membranes. Phys. Rev. Lett. 82, 4356–4359 (1999).",{"doi":1494},"10.1103\u002FPhysRevLett.82.4356",{"id":24,"text":1496,"url":24,"identifiers":1497},"Betz, T., Lenz, M., Joanny, J. F. & Sykes, C. ATP-dependent mechanics of red blood cells. Proc. Natl Acad. Sci. USA 106, 15320–15325 (2009).",{"doi":1498},"10.1073\u002Fpnas.0904614106",{"id":24,"text":1500,"url":24,"identifiers":1501},"le Duc, Q. et al. Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner. J. Cell Biol. 189, 1107–1115 (2010).",{"doi":1502},"10.1083\u002Fjcb.201001149",{"id":24,"text":1504,"url":24,"identifiers":1505},"Heisenberg, C.-P. & Bellaïche, Y. Forces in tissue morphogenesis and patterning. Cell 153, 948–962 (2013).",{"doi":1506},"10.1016\u002Fj.cell.2013.05.008",{"id":24,"text":1508,"url":24,"identifiers":1509},"Sonnemann, K. J. & Bement, W. M. Wound repair: toward understanding and integration of single-cell and multicellular wound responses. Annu. Rev. Cell Dev. Biol. 27, 237–263 (2011).",{"doi":1510},"10.1146\u002Fannurev-cellbio-092910-154251",{"id":24,"text":1512,"url":24,"identifiers":1513},"Friedl, P. & Gilmour, D. Collective cell migration in morphogenesis, regeneration and cancer. Nat. Rev. Mol. Cell Biol. 10, 445–457 (2009).",{"doi":1514},"10.1038\u002Fnrm2720",{"id":24,"text":1516,"url":24,"identifiers":1517},"Sedzinski, J. et al. Polar actomyosin contractility destabilizes the position of the cytokinetic furrow. Nature 476, 462–466 (2011).",{"doi":1518},"10.1038\u002Fnature10286",{"id":24,"text":1520,"url":24,"identifiers":1521},"Tinevez, J.-Y. et al. Role of cortical tension in bleb growth. Proc. Natl Acad. Sci. 106, 18581–18586 (2009).",{"doi":1522},"10.1073\u002Fpnas.0903353106",{"id":24,"text":1524,"url":24,"identifiers":1525},"Rubinstein, B. et al. Actin–myosin viscoelastic flow in the keratocyte lamellipod. Biophys. J. 97, 1853–1863 (2009).",{"doi":1526},"10.1016\u002Fj.bpj.2009.07.020",{"id":24,"text":1528,"url":24,"identifiers":1529},"Kruse, K., Joanny, J. F., Julicher, F. & Prost, J. Contractility and retrograde flow in lamellipodium motion. Phys. Biol. 3, 130–137 (2006).",{"doi":1530},"10.1088\u002F1478-3975\u002F3\u002F2\u002F005",{"id":24,"text":1532,"url":24,"identifiers":1533},"Mertz, A. F. et al. Cadherin-based intercellular adhesions organize epithelial cell–matrix traction forces. Proc. Natl Acad. Sci. USA 110, 842–847 (2012).",{"doi":1534},"10.1073\u002Fpnas.1217279110",{"id":24,"text":1536,"url":24,"identifiers":1537},"Goehring, N. W. et al. Polarization of PAR proteins by advective triggering of a pattern-forming system. Science 334, 1137–1141 (2011).",{"doi":1538},"10.1126\u002Fscience.1208619",{"id":24,"text":1540,"url":24,"identifiers":1541},"Oakes, P. W., Banerjee, S., Marchetti, M. C. & Gardel, M. L. Geometry regulates traction stresses in adherent cells. Biophys. J. 107, 825–833 (2014).",{"doi":1542},"10.1016\u002Fj.bpj.2014.06.045",{"id":24,"text":1544,"url":24,"identifiers":1545},"Guthardt Torres, P., Bischofs, I. B. & Schwarz, U. S. Contractile network models for adherent cells. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 85, 011913 (2012).",{"doi":1546},"10.1103\u002FPhysRevE.85.011913",{"id":24,"text":1548,"url":24,"identifiers":1549},"Howard, J. Mechanics of Motor Proteins and the Cytoskeleton (Sinauer Associates, 2001).",{},{"id":24,"text":1551,"url":24,"identifiers":1552},"Yao, Norman, Y. et al. Stress-enhanced gelation: A dynamic nonlinearity of elasticity. Phys. Rev. Lett. 110, 018103 (2013).",{"doi":1553},"10.1103\u002FPhysRevLett.110.018103",{"id":24,"text":1555,"url":24,"identifiers":1556},"Verkhovsky, A. B., Svitkina, T. M. & Borisy, G. G. Self-polarization and directional motility of cytoplasm. Curr. Biol. 9, 11–20 (1999).",{"doi":1557},"10.1016\u002FS0960-9822(99)80042-6",{"id":24,"text":1559,"url":24,"identifiers":1560},"Sun, S. X., Walcott, S. & Wolgemuth, C. W. Cytoskeletal cross-linking and bundling in motor-independent contraction. Curr. Biol. 20, R649–R654 (2010).",{"doi":1561},"10.1016\u002Fj.cub.2010.07.004",{"id":24,"text":1563,"url":24,"identifiers":1564},"Ramaswamy, S. The mechanics and statistics of active matter. Annu. Rev. Condensed Matter Phys. 1, 323–345 (2010).",{"doi":1565},"10.1146\u002Fannurev-conmatphys-070909-104101",{"id":24,"text":1567,"url":24,"identifiers":1568},"Bartles, J. R. Parallel actin bundles and their multiple actin-bundling proteins. Curr. Opin. Cell Biol. 12, 72–78 (2000).",{"doi":1569},"10.1016\u002FS0955-0674(99)00059-9",{"id":24,"text":1571,"url":24,"identifiers":1572},"Kohler, S. & Bausch, A. R. Contraction mechanisms in composite active actin networks. PLoS ONE 7, e39869 (2012).",{"doi":1573},"10.1371\u002Fjournal.pone.0039869",{"id":24,"text":1575,"url":24,"identifiers":1576},"Kane, R. E. Interconversion of structural and contractile actin gels by insertion of myosin during assembly. J. Cell Biol. 97, 1745–1752 (1983).",{"doi":1577},"10.1083\u002Fjcb.97.6.1745",{"id":24,"text":1579,"url":24,"identifiers":1580},"Backouche, F., Haviv, L., Groswasser, D. & Bernheim-Groswasser, A. Active gels: dynamics of patterning and self-organization. Phys. Biol. 3, 264–273 (2006).",{"doi":1581},"10.1088\u002F1478-3975\u002F3\u002F4\u002F004",{"id":24,"text":1583,"url":24,"identifiers":1584},"Aratyn, Y. S., Schaus, T. E., Taylor, E. W. & Borisy, G. G. Intrinsic dynamic behavior of fascin in filopodia. Mol. Biol. Cell 18, 3928–3940 (2007).",{"doi":1585},"10.1091\u002Fmbc.e07-04-0346",{"id":24,"text":1587,"url":24,"identifiers":1588},"Wang, K., Ash, J. F. & Singer, S. J. Filamin, a new high-molecular-weight protein found in smooth muscle and non-muscle cells. Proc. Natl Acad. Sci. USA 72, 4483–4486 (1975).",{"doi":1589},"10.1073\u002Fpnas.72.11.4483",{"id":24,"text":1591,"url":24,"identifiers":1592},"Biro, Maté et al. Cell cortex composition and homeostasis resolved by integrating proteomics and quantitative imaging. Cytoskeleton 70, 741–754 (2013).",{"doi":1593},"10.1002\u002Fcm.21142",{"id":24,"text":1595,"url":24,"identifiers":1596},"Schmoller, K. M., Lieleg, O. & Bausch, A. R. Structural and viscoelastic properties of actin\u002Ffilamin networks: cross-linked versus bundled networks. Biophys. J. 97, 83–89 (2009).",{"doi":1597},"10.1016\u002Fj.bpj.2009.04.040",{"id":24,"text":1599,"url":24,"identifiers":1600},"Kasza, K. E. et al. Actin filament length tunes elasticity of flexibly cross-linked actin networks. Biophys. J. 99, 1091–1100 (2010).",{"doi":1601},"10.1016\u002Fj.bpj.2010.06.025",{"id":24,"text":1603,"url":24,"identifiers":1604},"Kohler, S., Schmoller, K. M., Crevenna, A. H. & Bausch, A. R. Regulating contractility of the actomyosin cytoskeleton by pH. Cell Rep. 2, 433–439 (2012).",{"doi":1605},"10.1016\u002Fj.celrep.2012.08.014",{"id":24,"text":1607,"url":24,"identifiers":1608},"Goldmann, W. H. & Isenberg, G. Analysis of filamin and α-actinin binding to actin by the stopped flow method. FEBS Lett. 336, 408–410 (1993).",{"doi":1609},"10.1016\u002F0014-5793(93)80847-N",{"id":24,"text":1611,"url":24,"identifiers":1612},"Ebashi, S. & Ebashi, F. α-actinin, a new structural protein from striated muscle. I. Preparation and action on actomyosin-ATP interaction. J. Biochem. 58, 7–12 (1965).",{"doi":1613},"10.1093\u002Foxfordjournals.jbchem.a128167",{"id":24,"text":1615,"url":24,"identifiers":1616},"Edlund, M., Lotano, M. A. & Otey, C. A. Dynamics of α-actinin in focal adhesions and stress fibers visualized with α-actinin–green fluorescent protein. Cell. Motil. Cytoskeleton 48, 190–200 (2001).",{"doi":1617},"10.1002\u002F1097-0169(200103)48:3\u003C190::AID-CM1008>3.0.CO;2-C",{"id":24,"text":1619,"url":24,"identifiers":1620},"Sanger, J. M., Mittal, B., Pochapin, M. B. & Sanger, J. W. Stress fiber and cleavage furrow formation in living cells microinjected with fluorescently labeled α-actinin. Cell. Motil. Cytoskeleton 7, 209–220 (1987).",{"doi":1621},"10.1002\u002Fcm.970070304",{"id":24,"text":1623,"url":24,"identifiers":1624},"Falzone, T. T., Lenz, M., Kovar, D. R. & Gardel, M. L. Assembly kinetics determine the architecture of α-actinin crosslinked F-actin networks. Nat. Commun. 3, 861 (2012).",{"doi":1625},"10.1038\u002Fncomms1862",{"id":24,"text":1627,"url":24,"identifiers":1628},"Field, C. M. & Alberts, B. M. Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex. J. Cell Biol. 131, 165–178 (1995).",{"doi":1629},"10.1083\u002Fjcb.131.1.165",{"id":24,"text":1631,"url":24,"identifiers":1632},"Schaller, V. et al. Crosslinking proteins modulate the self-organization of driven systems. Soft Matter 9, 7229–7233 (2013).",{"doi":1633},"10.1039\u002Fc3sm50506e",{"id":24,"text":1635,"url":24,"identifiers":1636},"Kinoshita, M. et al. Self- and actin-templated assembly of Mammalian septins. Dev. Cell 3, 791–802 (2002).",{"doi":1637},"10.1016\u002FS1534-5807(02)00366-0",{"id":24,"text":1639,"url":24,"identifiers":1640},"Reichl, E. M. et al. Interactions between myosin and actin crosslinkers control cytokinesis contractility dynamics and mechanics. Curr. Biol. 18, 471–480 (2008).",{"doi":1641},"10.1016\u002Fj.cub.2008.02.056",{"id":24,"text":1643,"url":24,"identifiers":1644},"Weber, I. et al. Two-step positioning of a cleavage furrow by cortexillin and myosin II. Curr. Biol. 10, 501–506 (2000).",{"doi":1645},"10.1016\u002FS0960-9822(00)00452-8",{"id":24,"text":1647,"url":24,"identifiers":1648},"Yin, H. L. & Stossel, T. P. Control of cytoplasmic actin gel–sol transformation by gelsolin, a calcium-dependent regulatory protein. Nature 281, 583–586 (1979).",{"doi":1649},"10.1038\u002F281583a0",{"id":24,"text":1651,"url":24,"identifiers":1652},"Murrell, M. et al. Spreading dynamics of biomimetic actin cortices. Biophys. J. 100, 1400–1409 (2011).",{"doi":1653},"10.1016\u002Fj.bpj.2011.01.038",{"id":24,"text":1655,"url":24,"identifiers":1656},"Murrell, M. & Gardel, M. L. Actomyosin sliding is attenuated in contractile biomimetic cortices. Mol. Biol. Cell 25, 1845–1853 (2014).",{"doi":1657},"10.1091\u002Fmbc.e13-08-0450",{"id":24,"text":1659,"url":24,"identifiers":1660},"Carvalho, K. et al. Cell-sized liposomes reveal how actomyosin cortical tension drives shape change. Proc. Natl Acad. Sci. USA 110, 16456–16461 (2013).",{"doi":1661},"10.1073\u002Fpnas.1221524110",{"id":1663,"createTime":1664,"updateTime":1665,"relativeEntities":1666,"slug":1667,"properties":1668,"entityType":131,"verifyStatus":132,"verifyTime":1680,"verifyNote":133,"languages":1681,"translateLanguages":24,"viewCount":25,"primaryUrl":1682,"fullTextUrl":24,"authors":1683,"publicationType":174,"publisherRelationship":1737,"citationCount":1792,"citationInfo":1793,"publishDate":1797,"publishYear":1794,"citationAnalyzeStatus":247,"lastCitationAnalyze":1798,"indexDatabases":1799,"openAccess":24,"references":1800,"isForceReanalyzing":409},"c66fab85-7f15-4512-80cc-66c2c2ae665c","2024-12-18T20:11:30.053+00:00","2026-03-09T04:51:39.927+00:00",[],"Peroxisomal-protein-import-and-ERAD-variations-on-a-common-theme",{"openalex":1669,"mag":1671,"title":1673,"gsPaper":1675,"pm":1676,"doi":1678},{"VOID":1670},"W2041810719",{"VOID":1672},"2041810719",{"EN":1674},"Peroxisomal protein import and ERAD: variations on a common theme",{"VOID":126},{"VOID":1677},"21081964",{"VOID":1679},"10.1038\u002Fnrm3008","2024-12-18T20:11:30.052+00:00",[135],"https:\u002F\u002Fwww.nature.com\u002Farticles\u002Fnrm3008",[1684,1703,1720],{"id":1685,"sortIndex":25,"researcher":24,"roles":1686,"affiliations":1687,"properties":1696,"displayName":1700,"givenName":24,"familyName":24},"1e64a58f-4ec2-4e86-839f-1e71a35044f1",[],[1688],{"id":1689,"sortIndex":25,"affiliation":1690,"properties":24},"e0bc993d-43b6-4bf9-a1d9-e208c21b6a6b",{"id":1689,"createTime":24,"updateTime":24,"relativeEntities":1691,"slug":24,"properties":1692,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":1695,"statistic":24},[],{"title":1693},{"EN":1694},"Ruhr-Universität Bochum, Medizinische Fakultät, Institut für Physiologische Chemie, Abteilung für Systembiochemie, Universitätsstraße 150, D-44780 Bochum, Germany.",[],{"orcid":1697,"title":1699,"openalex":1701},{"VOID":1698},"https:\u002F\u002Forcid.org\u002F0000-0003-2762-3403",{"EN":1700},"Wolfgang Schliebs",{"VOID":1702},"A5012995576",{"id":1704,"sortIndex":99,"researcher":24,"roles":1705,"affiliations":1706,"properties":1715,"displayName":1717,"givenName":24,"familyName":24},"71575e2a-3e88-4ac0-aeb1-40b4a8c0b2f8",[],[1707],{"id":1708,"sortIndex":25,"affiliation":1709,"properties":24},"8a7296fc-c0a3-4c82-90d8-b961241e5b25",{"id":1708,"createTime":24,"updateTime":24,"relativeEntities":1710,"slug":24,"properties":1711,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":1714,"statistic":24},[],{"title":1712},{"EN":1713},"Abteilung für Systembiochemie, Wolfgang Schliebs, Wolfgang Girzalsky and Ralf Erdmann are at the Ruhr-Universität Bochum, Medizinische Fakultät, Institut für Physiologische Chemie, Universitätsstraße 150, D-44780 Bochum, Germany.,",[],{"title":1716,"openalex":1718},{"EN":1717},"Wolfgang Girzalsky",{"VOID":1719},"A5035628092",{"id":1721,"sortIndex":1016,"researcher":24,"roles":1722,"affiliations":1723,"properties":1730,"displayName":1734,"givenName":24,"familyName":24},"c119d577-b346-4d23-8c6a-c5df6a6b9a9e",[],[1724],{"id":1708,"sortIndex":25,"affiliation":1725,"properties":24},{"id":1708,"createTime":24,"updateTime":24,"relativeEntities":1726,"slug":24,"properties":1727,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":1729,"statistic":24},[],{"title":1728},{"EN":1713},[],{"orcid":1731,"title":1733,"openalex":1735},{"VOID":1732},"https:\u002F\u002Forcid.org\u002F0000-0001-8380-0342",{"EN":1734},"Ralf Erdmann",{"VOID":1736},"A5037710435",{"url":24,"publisher":1738,"properties":1785},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1739,"slug":10,"properties":1740,"entityType":22,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":25,"subjectFields":1745,"manageAffiliations":1754,"indexDatabases":1765,"url":90,"thumbnailPath":24,"statistic":1780,"gsStatistic":24,"type":24,"analyzePriority":24},[],{"country":1741,"eissn":1742,"issn":1743,"title":1744},{"VOID":13},{"VOID":15},{"VOID":17},{"EN":19},[1746,1750],{"id":28,"createTime":24,"updateTime":24,"relativeEntities":1747,"label":1748,"description":1749,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":31},{},{"id":34,"createTime":24,"updateTime":24,"relativeEntities":1751,"label":1752,"description":1753,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":37},{},[1755,1760],{"id":41,"createTime":24,"updateTime":24,"relativeEntities":1756,"slug":24,"properties":1757,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":1759,"statistic":24},[],{"title":1758},{"EN":45},[],{"id":48,"createTime":24,"updateTime":24,"relativeEntities":1761,"slug":24,"properties":1762,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":1764,"statistic":24},[],{"title":1763},{"EN":52},[],[1766,1773],{"id":56,"indexDatabase":1767,"url":69,"indexYears":24,"academicFieldIds":1772,"indexDatabaseRanking":24},{"id":58,"createTime":24,"updateTime":24,"relativeEntities":1768,"label":1769,"description":1770,"key":65,"publicationTags":1771,"standard":24},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":1774,"url":84,"indexYears":85,"academicFieldIds":1779,"indexDatabaseRanking":89},{"id":75,"createTime":24,"updateTime":24,"relativeEntities":1775,"label":1776,"description":1777,"key":81,"publicationTags":1778,"standard":24},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88],{"impactFactor":25,"impactFactorByYear":1781,"i10Index":97,"i10IndexLast5Year":25,"totalPublication":97,"totalPublicationByYear":1782,"totalCitation":100,"totalCitationByYear":1783,"totalCitationPerPublication":106,"totalCitationPerPublicationByYear":1784,"hindexLast5Year":97,"hindex":97},{"2016":93,"2017":94,"2019":95,"2020":96},{"2007":99,"2009":99,"2015":99,"2018":99},{"2007":102,"2009":103,"2015":104,"2018":105},{"2007":102,"2009":103,"2015":104,"2018":105},{"issue":1786,"pages":1788,"volume":1790},{"VOID":1787},"12",{"VOID":1789},"885-890",{"VOID":1791},"11",114,{"total":1792,"publishYear":1794,"statisticByYear":1795},2010,{"2012":1796,"2013":237,"2014":242,"2015":237,"2016":538,"2017":245,"2018":1016,"2019":1036,"2020":97,"2021":99,"2022":537,"2023":245,"2024":1016},11,"2010-12-01","2026-03-09T04:51:39.926+00:00",[67,89],[1801,1805,1809,1813,1817,1821,1825,1829,1833,1837,1841,1845,1849,1853,1857,1861,1865,1869,1873,1877,1881,1885,1889,1893,1897,1901,1905,1909,1913,1917,1921,1925,1929,1933,1937,1941,1945,1949,1953,1957,1961,1965,1969,1973,1977,1981,1985,1989,1993,1997,2001,2005,2009,2012,2016,2020,2024,2028],{"id":24,"text":1802,"url":24,"identifiers":1803},"McNew, J. A. & Goodman, J. M. An oligomeric protein is imported into peroxisomes in vivo. J. Cell Biol. 127, 1245–1257 (1994).",{"doi":1804},"10.1083\u002Fjcb.127.5.1245",{"id":24,"text":1806,"url":24,"identifiers":1807},"Glover, J. R., Andrews, D. W. & Rachubinski, R. A. Saccharomyces cerevisiae peroxisomal thiolase is imported as a dimer. Proc. Natl Acad. Sci. USA 91, 10541–10545 (1994).",{"doi":1808},"10.1073\u002Fpnas.91.22.10541",{"id":24,"text":1810,"url":24,"identifiers":1811},"Häusler, T., Stierhof, Y. D., Wirtz, E. & Clayton, C. Import of a DHFR Hybrid protein into gycosomes in vivo is not inhibited by the folate-analogue aminopterin. J. Cell Biol. 132, 311–324 (1996).",{"doi":1812},"10.1083\u002Fjcb.132.3.311",{"id":24,"text":1814,"url":24,"identifiers":1815},"Brown, L. A. & Baker, A. Shuttles and cycles: transport of proteins into the peroxisome matrix. Mol. Membr. Biol. 25, 363–375 (2008).",{"doi":1816},"10.1080\u002F09687680802130583",{"id":24,"text":1818,"url":24,"identifiers":1819},"Brocard, C. & Hartig, A. Peroxisome targeting signal 1: is it really a simple tripeptide? Biochim. Biophys. Acta 1763, 1565–1573 (2006).",{"doi":1820},"10.1016\u002Fj.bbamcr.2006.08.022",{"id":24,"text":1822,"url":24,"identifiers":1823},"Schliebs, W. & Kunau, W. H. PTS2 co-receptors: diverse proteins with common features. Biochim. Biophys. Acta 1763, 1605–1612 (2006).",{"doi":1824},"10.1016\u002Fj.bbamcr.2006.08.051",{"id":24,"text":1826,"url":24,"identifiers":1827},"Stanley, W. A. et al. Recognition of a functional peroxisome type 1 target by the dynamic import receptor Pex5p. Mol. Cell 24, 653–663 (2006).",{"doi":1828},"10.1016\u002Fj.molcel.2006.10.024",{"id":24,"text":1830,"url":24,"identifiers":1831},"Girzalsky, W., Saffian, D. & Erdmann, R. Peroxisomal protein translocation. Biochim. Biophys. Acta 1803, 724–731 (2010).",{"doi":1832},"10.1016\u002Fj.bbamcr.2010.01.002",{"id":24,"text":1834,"url":24,"identifiers":1835},"Schnell, D. J. & Hebert, D. N. Protein translocons: multifunctional mediators of protein translocation across membranes. Cell 112, 491–505 (2003).",{"doi":1836},"10.1016\u002FS0092-8674(03)00110-7",{"id":24,"text":1838,"url":24,"identifiers":1839},"Erdmann, R. & Schliebs, W. Peroxisomal matrix protein import: the transient pore model. Nature Rev. Mol. Cell Biol. 6, 738–742 (2005).",{"doi":1840},"10.1038\u002Fnrm1710",{"id":24,"text":1842,"url":24,"identifiers":1843},"Dammai, V. & Subramani, S. The human peroxisomal targeting signal receptor, Pex5p, is translocated into the peroxisomal matrix and recycled to the cytosol. Cell 105, 187–196 (2001).",{"doi":1844},"10.1016\u002FS0092-8674(01)00310-5",{"id":24,"text":1846,"url":24,"identifiers":1847},"Ma, C., Schumann, U., Rayapuram, N. & Subramani, S. The peroxisomal matrix import of Pex8p requires only PTS receptors and Pex14p. Mol. Biol. Cell 20, 3680–3689 (2009).",{"doi":1848},"10.1091\u002Fmbc.e09-01-0037",{"id":24,"text":1850,"url":24,"identifiers":1851},"Meinecke, M. et al. The peroxisomal importomer constitutes a large and highly dynamic pore. Nature Cell Biol. 12, 273–277 (2010).",{"doi":1852},"10.1038\u002Fncb2027",{"id":24,"text":1854,"url":24,"identifiers":1855},"Gouveia, A. M., Reguenga, C., Oliveira, M. E., Sa-Miranda, C. & Azevedo, J. E. Characterization of peroxisomal Pex5p from rat liver: Pex5p in the Pex5p-Pex14p membrane complex is a transmembrane protein. J. Biol. Chem. 275, 32444–32451 (2000).",{"doi":1856},"10.1074\u002Fjbc.M004366200",{"id":24,"text":1858,"url":24,"identifiers":1859},"Platta, H. W., Grunau, S., Rosenkranz, K., Girzalsky, W. & Erdmann, R. Functional role of the AAA peroxins in dislocation of the cycling PTS1 receptor back to the cytosol. Nature Cell Biol. 7, 817–822 (2005).",{"doi":1860},"10.1038\u002Fncb1281",{"id":24,"text":1862,"url":24,"identifiers":1863},"Miyata, N. & Fujiki, Y. Shuttling mechanism of peroxisome targeting signal type 1 receptor Pex5: ATP-independent import and ATP-dependent export. Mol. Cell Biol. 25, 10822–10832 (2005).",{"doi":1864},"10.1128\u002FMCB.25.24.10822-10832.2005",{"id":24,"text":1866,"url":24,"identifiers":1867},"Matsumoto, N., Tamura, S. & Fujiki, Y. The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes. Nature Cell Biol. 5, 454–460 (2003).",{"doi":1868},"10.1038\u002Fncb982",{"id":24,"text":1870,"url":24,"identifiers":1871},"Birschmann, I. et al. Pex15p of Saccharomyces cerevisiae provides a molecular basis for recruitment of the AAA Peroxin Pex6p to peroxisomal membranes. Mol. Biol. Cell 14, 2226–2236 (2003).",{"doi":1872},"10.1091\u002Fmbc.e02-11-0752",{"id":24,"text":1874,"url":24,"identifiers":1875},"Platta, H. W. et al. Ubiquitination of the peroxisomal import receptor Pex5p is required for its recycling. J. Cell Biol. 177, 197–204 (2007).",{"doi":1876},"10.1083\u002Fjcb.200611012",{"id":24,"text":1878,"url":24,"identifiers":1879},"Carvalho, A. F. et al. Ubiquitination of mammalian Pex5p, the peroxisomal import receptor. J. Biol. Chem. 282, 31267–31272 (2007).",{"doi":1880},"10.1074\u002Fjbc.M706325200",{"id":24,"text":1882,"url":24,"identifiers":1883},"Platta, H. W. et al. Pex2 and Pex12 function as protein-ubiquitin ligases in peroxisomal protein import Mol. Cell Biol. 29, 5505–5516 (2009).",{"doi":1884},"10.1128\u002FMCB.00388-09",{"id":24,"text":1886,"url":24,"identifiers":1887},"Williams, C., van den Berg, M., Geers, E. & Distel, B. Pex10p functions as an E3 ligase for the Ubc4p-dependent ubiquitination of Pex5p. Biochem. Biophys. Res. Commun. 374, 620–624 (2008).",{"doi":1888},"10.1016\u002Fj.bbrc.2008.07.054",{"id":24,"text":1890,"url":24,"identifiers":1891},"Kiel, J. A., Emmrich, K., Meyer, H. E. & Kunau, W. H. Ubiquitination of the PTS1 receptor, Pex5p, suggests the presence of a quality control mechanism during peroxisomal matrix protein import. J. Biol. Chem. 280, 1921–1930 (2005).",{"doi":1892},"10.1074\u002Fjbc.M403632200",{"id":24,"text":1894,"url":24,"identifiers":1895},"Platta, H. W., Girzalsky, W. & Erdmann, R. Ubiquitination of the peroxisomal import receptor Pex5p. Biochem. J. 384, 37–45 (2004).",{"doi":1896},"10.1042\u002FBJ20040572",{"id":24,"text":1898,"url":24,"identifiers":1899},"Purdue, P. E. & Lazarow, P. B. Pex18p is constitutively degraded during peroxisome biogenesis. J. Biol. Chem. 276, 47684–47689 (2001).",{"doi":1900},"10.1074\u002Fjbc.M106823200",{"id":24,"text":1902,"url":24,"identifiers":1903},"Leon, S. et al. Dynamics of the peroxisomal import cycle of PpPex20p: ubiquitin-dependent localization and regulation. J. Cell Biol. 172, 67–78 (2006).",{"doi":1904},"10.1083\u002Fjcb.200508096",{"id":24,"text":1906,"url":24,"identifiers":1907},"Leon, S. & Subramani, S. A conserved cysteine residue of Pichia pastoris Pex20p is essential for its recycling from the peroxisome to the cytosol. J. Biol. Chem. 282, 7424–7430 (2007).",{"doi":1908},"10.1074\u002Fjbc.M611627200",{"id":24,"text":1910,"url":24,"identifiers":1911},"Grou, C. P. et al. Members of the E2D (UbcH5) family mediate the ubiquitination of the conserved cysteine of Pex5p, the peroxisomal import receptor. J. Biol. Chem. 283, 14190–14197 (2008).",{"doi":1912},"10.1074\u002Fjbc.M800402200",{"id":24,"text":1914,"url":24,"identifiers":1915},"Grou, C. P. et al. Properties of the ubiquitin-Pex5p thiol ester conjugate. J. Biol. Chem. 284, 10504–10513 (2009).",{"doi":1916},"10.1074\u002Fjbc.M808978200",{"id":24,"text":1918,"url":24,"identifiers":1919},"Van den Berg, B. et al. X-ray structure of a protein-conducting channel. Nature 427, 36–44 (2004).",{"doi":1920},"10.1038\u002Fnature02218",{"id":24,"text":1922,"url":24,"identifiers":1923},"Rapoport, T. A. Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes. Nature 450, 663–669 (2007).",{"doi":1924},"10.1038\u002Fnature06384",{"id":24,"text":1926,"url":24,"identifiers":1927},"Nakatsukasa, K. & Brodsky, J. L. The recognition and retrotranslocation of misfolded proteins from the endoplasmic reticulum. Traffic 9, 861–870 (2008).",{"doi":1928},"10.1111\u002Fj.1600-0854.2008.00729.x",{"id":24,"text":1930,"url":24,"identifiers":1931},"Gauss, R., Sommer, T. & Jarosch, E. The Hrd1p ligase complex forms a linchpin between ER-lumenal substrate selection and Cdc48p recruitment. EMBO J. 25, 1827–1835 (2006).",{"doi":1932},"10.1038\u002Fsj.emboj.7601088",{"id":24,"text":1934,"url":24,"identifiers":1935},"Huyer, G. et al. Distinct machinery is required in Saccharomyces cerevisiae for the endoplasmic reticulum-associated degradation of a multispanning membrane protein and a soluble luminal protein. J. Biol. Chem. 279, 38369–38378 (2004).",{"doi":1936},"10.1074\u002Fjbc.M402468200",{"id":24,"text":1938,"url":24,"identifiers":1939},"Vashist, S. & Ng, D. T. Misfolded proteins are sorted by a sequential checkpoint mechanism of ER quality control. J. Cell Biol. 165, 41–52 (2004).",{"doi":1940},"10.1083\u002Fjcb.200309132",{"id":24,"text":1942,"url":24,"identifiers":1943},"Feldman, M. & van der Goot, F. G. Novel ubiquitin-dependent quality control in the endoplasmic reticulum. Trends Cell Biol. 19, 357–363 (2009).",{"doi":1944},"10.1016\u002Fj.tcb.2009.05.005",{"id":24,"text":1946,"url":24,"identifiers":1947},"Hirsch, C., Gauss, R., Horn, S. C., Neuber, O. & Sommer, T. The ubiquitylation machinery of the endoplasmic reticulum. Nature 458, 453–460 (2009).",{"doi":1948},"10.1038\u002Fnature07962",{"id":24,"text":1950,"url":24,"identifiers":1951},"Kreft, S. G., Wang, L. & Hochstrasser, M. Membrane topology of the yeast endoplasmic reticulum-localized ubiquitin ligase Doa10 and comparison with its human ortholog TEB4 (MARCH-VI). J. Biol. Chem. 281, 4646–4653 (2006).",{"doi":1952},"10.1074\u002Fjbc.M512215200",{"id":24,"text":1954,"url":24,"identifiers":1955},"Sommer, T. & Jentsch, S. A protein translocation defect linked to ubiquitin conjugation at the endoplasmic reticulum. Nature 365, 176–179 (1993).",{"doi":1956},"10.1038\u002F365176a0",{"id":24,"text":1958,"url":24,"identifiers":1959},"Biederer, T., Volkwein, C. & Sommer, T. Role of Cue1p in ubiquitination and degradation at the ER surface. Science 278, 1806–1809 (1997).",{"doi":1960},"10.1126\u002Fscience.278.5344.1806",{"id":24,"text":1962,"url":24,"identifiers":1963},"Deak, P. M. & Wolf, D. H. Membrane topology and function of Der3\u002FHrd1p as a ubiquitin-protein ligase (E3) involved in endoplasmic reticulum degradation. J. Biol. Chem. 276, 10663–10669 (2001).",{"doi":1964},"10.1074\u002Fjbc.M008608200",{"id":24,"text":1966,"url":24,"identifiers":1967},"Gauss, R., Jarosch, E., Sommer, T. & Hirsch, C. A complex of Yos9p and the HRD ligase integrates endoplasmic reticulum quality control into the degradation machinery. Nature Cell Biol. 8, 849–854 (2006).",{"doi":1968},"10.1038\u002Fncb1445",{"id":24,"text":1970,"url":24,"identifiers":1971},"Lilley, B. N. & Ploegh, H. L. A membrane protein required for dislocation of misfolded proteins from the ER. Nature 429, 834–840 (2004).",{"doi":1972},"10.1038\u002Fnature02592",{"id":24,"text":1974,"url":24,"identifiers":1975},"Wiertz, E. J. et al. Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction. Nature 384, 432–438 (1996).",{"doi":1976},"10.1038\u002F384432a0",{"id":24,"text":1978,"url":24,"identifiers":1979},"Ploegh, H. L. A lipid-based model for the creation of an escape hatch from the endoplasmic reticulum. Nature 448, 435–438 (2007).",{"doi":1980},"10.1038\u002Fnature06004",{"id":24,"text":1982,"url":24,"identifiers":1983},"Schuberth, C. & Buchberger, A. Membrane-bound Ubx2 recruits Cdc48 to ubiquitin ligases and their substrates to ensure efficient ER-associated protein degradation. Nature Cell Biol. 7, 999–1006 (2005).",{"doi":1984},"10.1038\u002Fncb1299",{"id":24,"text":1986,"url":24,"identifiers":1987},"Koller, A. et al. Pex22p of Pichia pastoris, essential for peroxisomal matrix protein import, anchors the ubiquitin-conjugating enzyme, Pex4p, on the peroxisomal membrane. J. Cell. Biol. 146, 99–112 (1999).",{"doi":1988},"10.1083\u002Fjcb.146.1.99",{"id":24,"text":1990,"url":24,"identifiers":1991},"Schuberth, C., Richly, H., Rumpf, S. & Buchberger, A. Shp1 and Ubx2 are adaptors of Cdc48 involved in ubiquitin-dependent protein degradation. EMBO Rep. 5, 818–824 (2004).",{"doi":1992},"10.1038\u002Fsj.embor.7400203",{"id":24,"text":1994,"url":24,"identifiers":1995},"Kerssen, D. et al. Membrane association of the cycling peroxisome import receptor Pex5p. J. Biol. Chem. 281, 27003–27015 (2006).",{"doi":1996},"10.1074\u002Fjbc.M509257200",{"id":24,"text":1998,"url":24,"identifiers":1999},"Gouveia, A. M., Guimarães, C. P., Oliveira, M. E., Sá- Miranda, C. & Azevedo, J. E. Insertion of Pex5p into the peroxisomal membrane is cargo protein-dependent. J. Biol. Chem. 278, 4389–4392 (2002).",{"doi":2000},"10.1074\u002Fjbc.C200650200",{"id":24,"text":2002,"url":24,"identifiers":2003},"Wanders, R. J. Metabolic and molecular basis of peroxisomal disorders: a review. Am. J. Med. Genet. A. 126, 355–375 (2004).",{"doi":2004},"10.1002\u002Fajmg.a.20661",{"id":24,"text":2006,"url":24,"identifiers":2007},"Imai, Y. et al. CHIP is associated with parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity. Mol. Cell 10, 55–67 (2002).",{"doi":2008},"10.1016\u002FS1097-2765(02)00583-X",{"id":24,"text":2010,"url":24,"identifiers":2011},"Gelman, M. S. & Kopito, R. R. Cystic fibrosis: premature degradation of mutant proteins as a molecular disease mechanism. Methods Mol. Biol. 232, 27–37 (2003).",{},{"id":24,"text":2013,"url":24,"identifiers":2014},"Kerscher, O., Felberbaum, R. & Hochstrasser, M. Modification of proteins by ubiquitin and ubiquitin-like proteins. Annu. Rev. Cell Dev. Biol. 22, 159–180 (2006).",{"doi":2015},"10.1146\u002Fannurev.cellbio.22.010605.093503",{"id":24,"text":2017,"url":24,"identifiers":2018},"Raiborg, C. & Stenmark, H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature 458, 445–452 (2009).",{"doi":2019},"10.1038\u002Fnature07961",{"id":24,"text":2021,"url":24,"identifiers":2022},"Hanson, P. I. & Whiteheart, S. W. AAA+ proteins: have engine, will work. Nature Rev. Mol. Cell Biol. 6, 519–529 (2005).",{"doi":2023},"10.1038\u002Fnrm1684",{"id":24,"text":2025,"url":24,"identifiers":2026},"Erzberger, J. P. & Berger, J. M. Evolutionary relationships and structural mechanisms of AAA+ proteins. Annu. Rev. Biophys. Biomol. Struct. 35, 95–114 (2006).",{"doi":2027},"10.1146\u002Fannurev.biophys.35.040405.101933",{"id":24,"text":2029,"url":24,"identifiers":2030},"Snider, J., Thibault, G. & Houry, W. A. The AAA+ superfamily of functionally diverse proteins. Genome Biol. 9, 216 (2008).",{"doi":2031},"10.1186\u002Fgb-2008-9-4-216",{"id":2033,"createTime":2034,"updateTime":2034,"relativeEntities":2035,"slug":2036,"properties":2037,"entityType":131,"verifyStatus":132,"verifyTime":2034,"verifyNote":133,"languages":2050,"translateLanguages":24,"viewCount":25,"primaryUrl":2051,"fullTextUrl":24,"authors":2052,"publicationType":174,"publisherRelationship":2089,"citationCount":2144,"citationInfo":2145,"publishDate":2153,"publishYear":2146,"citationAnalyzeStatus":23,"lastCitationAnalyze":24,"indexDatabases":2154,"openAccess":24,"references":2155,"isForceReanalyzing":409},"9f1ca759-caf3-498f-b970-84109eecf7fc","2025-02-11T01:31:58.654+00:00",[],"Diversity-and-versatility-of-p38-kinase-signalling-in-health-and-disease",{"openalex":2038,"mag":2040,"title":2042,"pm":2044,"doi":2046,"pmc":2048},{"VOID":2039},"W3122470240",{"VOID":2041},"3122470240",{"EN":2043},"Diversity and versatility of p38 kinase signalling in health and disease",{"VOID":2045},"33504982",{"VOID":2047},"10.1038\u002Fs41580-020-00322-w",{"VOID":2049},"7838852",[135],"https:\u002F\u002Fwww.nature.com\u002Farticles\u002Fs41580-020-00322-w",[2053,2072],{"id":2054,"sortIndex":25,"researcher":24,"roles":2055,"affiliations":2056,"properties":2065,"displayName":2069,"givenName":24,"familyName":24},"b6700a94-8ed4-4509-984c-fb67dac90e05",[],[2057],{"id":2058,"sortIndex":25,"affiliation":2059,"properties":24},"2cb8306d-e913-428d-9720-9ab654eade7a",{"id":2058,"createTime":24,"updateTime":24,"relativeEntities":2060,"slug":24,"properties":2061,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":2064,"statistic":24},[],{"title":2062},{"VI":2063},"Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain",[],{"orcid":2066,"title":2068,"openalex":2070},{"VOID":2067},"https:\u002F\u002Forcid.org\u002F0000-0002-2546-0295",{"EN":2069},"Begoña Cánovas",{"VOID":2071},"A5007370352",{"id":2073,"sortIndex":99,"researcher":24,"roles":2074,"affiliations":2075,"properties":2082,"displayName":2086,"givenName":24,"familyName":24},"d18d9c71-89b6-4cc1-a800-d8176db983e3",[],[2076],{"id":2058,"sortIndex":25,"affiliation":2077,"properties":24},{"id":2058,"createTime":24,"updateTime":24,"relativeEntities":2078,"slug":24,"properties":2079,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":2081,"statistic":24},[],{"title":2080},{"VI":2063},[],{"orcid":2083,"title":2085,"openalex":2087},{"VOID":2084},"https:\u002F\u002Forcid.org\u002F0000-0002-7631-4060",{"EN":2086},"Ángel R. Nebreda",{"VOID":2088},"A5064241770",{"url":24,"publisher":2090,"properties":2137},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":2091,"slug":10,"properties":2092,"entityType":22,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":25,"subjectFields":2097,"manageAffiliations":2106,"indexDatabases":2117,"url":90,"thumbnailPath":24,"statistic":2132,"gsStatistic":24,"type":24,"analyzePriority":24},[],{"country":2093,"eissn":2094,"issn":2095,"title":2096},{"VOID":13},{"VOID":15},{"VOID":17},{"EN":19},[2098,2102],{"id":28,"createTime":24,"updateTime":24,"relativeEntities":2099,"label":2100,"description":2101,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":31},{},{"id":34,"createTime":24,"updateTime":24,"relativeEntities":2103,"label":2104,"description":2105,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":37},{},[2107,2112],{"id":41,"createTime":24,"updateTime":24,"relativeEntities":2108,"slug":24,"properties":2109,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":2111,"statistic":24},[],{"title":2110},{"EN":45},[],{"id":48,"createTime":24,"updateTime":24,"relativeEntities":2113,"slug":24,"properties":2114,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":2116,"statistic":24},[],{"title":2115},{"EN":52},[],[2118,2125],{"id":56,"indexDatabase":2119,"url":69,"indexYears":24,"academicFieldIds":2124,"indexDatabaseRanking":24},{"id":58,"createTime":24,"updateTime":24,"relativeEntities":2120,"label":2121,"description":2122,"key":65,"publicationTags":2123,"standard":24},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":2126,"url":84,"indexYears":85,"academicFieldIds":2131,"indexDatabaseRanking":89},{"id":75,"createTime":24,"updateTime":24,"relativeEntities":2127,"label":2128,"description":2129,"key":81,"publicationTags":2130,"standard":24},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88],{"impactFactor":25,"impactFactorByYear":2133,"i10Index":97,"i10IndexLast5Year":25,"totalPublication":97,"totalPublicationByYear":2134,"totalCitation":100,"totalCitationByYear":2135,"totalCitationPerPublication":106,"totalCitationPerPublicationByYear":2136,"hindexLast5Year":97,"hindex":97},{"2016":93,"2017":94,"2019":95,"2020":96},{"2007":99,"2009":99,"2015":99,"2018":99},{"2007":102,"2009":103,"2015":104,"2018":105},{"2007":102,"2009":103,"2015":104,"2018":105},{"issue":2138,"pages":2140,"volume":2142},{"VOID":2139},"5",{"VOID":2141},"346-366",{"VOID":2143},"22",393,{"total":2144,"publishYear":2146,"statisticByYear":2147},2021,{"2021":2148,"2022":2149,"2023":2150,"2024":2151,"2025":2152},46,98,104,132,10,"2021-05-01",[67,89],[2156,2160,2164,2168,2172,2176,2180,2184,2188,2192,2196,2200,2204,2208,2212,2216,2220,2224,2228,2232,2236,2240,2244,2248,2252,2256,2260,2264,2268,2272,2276,2280,2284,2288,2292,2296,2300,2304,2308,2312,2316,2320,2324,2328,2332,2336,2340,2344,2348,2352,2356,2360,2364,2368,2372,2376,2380,2384,2388,2392,2396,2400,2404,2408,2412,2416,2420,2424,2428,2432,2436,2440,2444,2448,2452,2456,2460,2464,2468,2472,2476,2480,2484,2488,2492,2496,2500,2504,2508,2512,2516,2520,2524,2528,2532,2535,2539,2543,2546,2550,2554,2558,2562,2566,2570,2574,2578,2582,2586,2590,2594,2598,2602,2606,2610,2614,2618,2622,2626,2630,2634,2638,2642,2646,2650,2654,2658,2662,2666,2670,2674,2678,2682,2686,2690,2694,2698,2702,2706,2710,2714,2718,2722,2726,2730,2734,2738,2742,2746,2750,2754,2758,2762,2766,2770,2774,2778,2782,2786,2790,2794,2798,2802,2806,2810,2814,2818,2822,2826,2830,2834,2838,2842,2846,2850,2854,2858,2862,2866,2870,2874,2878,2882,2886,2890,2894,2898,2902,2906,2910,2914,2918,2922,2926,2930,2934,2938,2942,2946,2950,2954,2958,2962,2966,2970,2974,2978,2982,2986,2990,2994,2998,3002,3006,3010,3014,3018,3022,3026,3030,3034,3038,3042,3046,3050,3054,3058,3062,3066,3070,3074,3078,3082,3086,3090,3094,3098,3102,3106,3110,3114,3118,3122,3126,3130,3134,3138,3142,3146,3150,3154,3158,3162,3166,3170,3174,3178,3182,3186,3190,3194,3198,3202,3206],{"id":24,"text":2157,"url":24,"identifiers":2158},"Cuenda, A. & Rousseau, S. p38 MAP-kinases pathway regulation, function and role in human diseases. Biochim. Biophys. Acta 1773, 1358–1375 (2007).",{"doi":2159},"10.1016\u002Fj.bbamcr.2007.03.010",{"id":24,"text":2161,"url":24,"identifiers":2162},"Wagner, E. F. & Nebreda, A. R. Signal integration by JNK and p38 MAPK pathways in cancer development. Nat. Rev. Cancer 9, 537–549 (2009).",{"doi":2163},"10.1038\u002Fnrc2694",{"id":24,"text":2165,"url":24,"identifiers":2166},"Cuadrado, A. & Nebreda, A. R. Mechanisms and functions of p38 MAPK signalling. Biochem. J. 429, 403–417 (2010).",{"doi":2167},"10.1042\u002FBJ20100323",{"id":24,"text":2169,"url":24,"identifiers":2170},"Kyriakis, J. M. & Avruch, J. Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol. Rev. 92, 689–737 (2012).",{"doi":2171},"10.1152\u002Fphysrev.00028.2011",{"id":24,"text":2173,"url":24,"identifiers":2174},"Hotamisligil, G. S. & Davis, R. J. Cell signaling and stress responses. Cold Spring Harb. Perspect. Biol. 8, a006072 (2016).",{"doi":2175},"10.1101\u002Fcshperspect.a006072",{"id":24,"text":2177,"url":24,"identifiers":2178},"Han, J., Wu, J. & Silke, J. An overview of mammalian p38 mitogen-activated protein kinases, central regulators of cell stress and receptor signaling. F1000Res. 9, 653 (2020).",{"doi":2179},"10.12688\u002Ff1000research.22092.1",{"id":24,"text":2181,"url":24,"identifiers":2182},"Cuenda, A. & Sanz-Ezquerro, J. J. p38γ and p38δ: from spectators to key physiological players. Trends Biochem. Sci. 42, 431–442 (2017). This extensive review addresses the functions of p38γ and p38δ.",{"doi":2183},"10.1016\u002Fj.tibs.2017.02.008",{"id":24,"text":2185,"url":24,"identifiers":2186},"Han, J., Lee, J. D., Bibbs, L. & Ulevitch, R. J. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265, 808–811 (1994).",{"doi":2187},"10.1126\u002Fscience.7914033",{"id":24,"text":2189,"url":24,"identifiers":2190},"Rouse, J. et al. A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell 78, 1027–1037 (1994).",{"doi":2191},"10.1016\u002F0092-8674(94)90277-1",{"id":24,"text":2193,"url":24,"identifiers":2194},"Freshney, N. W. et al. Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27. Cell 78, 1039–1049 (1994).",{"doi":2195},"10.1016\u002F0092-8674(94)90278-X",{"id":24,"text":2197,"url":24,"identifiers":2198},"Lee, J. C. et al. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 372, 739–746 (1994). Together with Han et al. (1994), Rouse et al. (1994) and Freshney et al. (1994), this paper reports the identification of the first mammalian p38 kinase using different experimental systems and approaches.",{"doi":2199},"10.1038\u002F372739a0",{"id":24,"text":2201,"url":24,"identifiers":2202},"Sudo, T., Yagasaki, Y., Hama, H., Watanabe, N. & Osada, H. Exip, a new alternative splicing variant of p38α, can induce an earlier onset of apoptosis in HeLa cells. Biochem. Biophys. Res. Commun. 291, 838–843 (2002).",{"doi":2203},"10.1006\u002Fbbrc.2002.6529",{"id":24,"text":2205,"url":24,"identifiers":2206},"Sanz, V., Arozarena, I. & Crespo, P. Distinct carboxy-termini confer divergent characteristics to the mitogen-activated protein kinase p38α and its splice isoform Mxi2. FEBS Lett. 474, 169–174 (2000).",{"doi":2207},"10.1016\u002FS0014-5793(00)01598-2",{"id":24,"text":2209,"url":24,"identifiers":2210},"Eyers, P. A., Craxton, M., Morrice, N., Cohen, P. & Goedert, M. Conversion of SB 203580-insensitive MAP kinase family members to drug-sensitive forms by a single amino-acid substitution. Chem. Biol. 5, 321–328 (1998).",{"doi":2211},"10.1016\u002FS1074-5521(98)90170-3",{"id":24,"text":2213,"url":24,"identifiers":2214},"Gum, R. J. et al. Acquisition of sensitivity of stress-activated protein kinases to the p38 inhibitor, SB 203580, by alteration of one or more amino acids within the ATP binding pocket. J. Biol. Chem. 273, 15605–15610 (1998).",{"doi":2215},"10.1074\u002Fjbc.273.25.15605",{"id":24,"text":2217,"url":24,"identifiers":2218},"Adams, R. H. et al. Essential role of p38α MAP kinase in placental but not embryonic cardiovascular development. Mol. Cell 6, 109–116 (2000).",{"doi":2219},"10.1016\u002FS1097-2765(05)00014-6",{"id":24,"text":2221,"url":24,"identifiers":2222},"Mudgett, J. S. et al. Essential role for p38α mitogen-activated protein kinase in placental angiogenesis. Proc. Natl Acad. Sci. USA 97, 10454–10459 (2000). Together with Adams et al. (2000), this paper provides in vivo evidence for a critical role of p38α in the regulation of a process unrelated to the acute stress response.",{"doi":2223},"10.1073\u002Fpnas.180316397",{"id":24,"text":2225,"url":24,"identifiers":2226},"Brancho, D. et al. Mechanism of p38 MAP kinase activation in vivo. Genes Dev. 17, 1969–1978 (2003).",{"doi":2227},"10.1101\u002Fgad.1107303",{"id":24,"text":2229,"url":24,"identifiers":2230},"Beardmore, V. A. et al. Generation and characterization of p38β (MAPK11) gene-targeted mice. Mol. Cell Biol. 25, 10454–104645 (2005).",{"doi":2231},"10.1128\u002FMCB.25.23.10454-10464.2005",{"id":24,"text":2233,"url":24,"identifiers":2234},"Greenblatt, M. B. et al. The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice. J. Clin. Invest. 120, 2457–2473 (2010).",{"doi":2235},"10.1172\u002FJCI42285",{"id":24,"text":2237,"url":24,"identifiers":2238},"del Barco Barrantes, I., Coya, J. M., Maina, F., Arthur, J. S. & Nebreda, A. R. Genetic analysis of specific and redundant roles for p38α and p38β MAPKs during mouse development. Proc. Natl Acad. Sci. USA 108, 12764–12769 (2011).",{"doi":2239},"10.1073\u002Fpnas.1015013108",{"id":24,"text":2241,"url":24,"identifiers":2242},"Arriazu, E. et al. A new regulatory mechanism of protein phosphatase 2A activity via SET in acute myeloid leukemia. Blood Cancer J. 10, 3 (2020).",{"doi":2243},"10.1038\u002Fs41408-019-0270-0",{"id":24,"text":2245,"url":24,"identifiers":2246},"Warr, N. et al. Gadd45γ and Map3k4 interactions regulate mouse testis determination via p38 MAPK-mediated control of Sry expression. Dev. Cell 23, 1020–1031 (2012).",{"doi":2247},"10.1016\u002Fj.devcel.2012.09.016",{"id":24,"text":2249,"url":24,"identifiers":2250},"Llopis, A. et al. The stress-activated protein kinases p38α\u002Fβ and JNK1\u002F2 cooperate with Chk1 to inhibit mitotic entry upon DNA replication arrest. Cell Cycle 11, 3627–3637 (2012).",{"doi":2251},"10.4161\u002Fcc.21917",{"id":24,"text":2253,"url":24,"identifiers":2254},"Hayakawa, M. et al. Loss of functionally redundant p38 isoforms in T cells enhances regulatory T cell induction. J. Biol. Chem. 292, 1762–1772 (2017).",{"doi":2255},"10.1074\u002Fjbc.M116.764548",{"id":24,"text":2257,"url":24,"identifiers":2258},"Escos, A., Risco, A., Alsina-Beauchamp, D. & Cuenda, A. p38γ and p38δ mitogen activated protein kinases (MAPKs), new stars in the MAPK galaxy. Front. Cell Dev. Biol. 4, 31 (2016).",{"doi":2259},"10.3389\u002Ffcell.2016.00031",{"id":24,"text":2261,"url":24,"identifiers":2262},"Matesanz, N. et al. p38α blocks brown adipose tissue thermogenesis through p38δ inhibition. PLoS Biol. 16, e2004455 (2018).",{"doi":2263},"10.1371\u002Fjournal.pbio.2004455",{"id":24,"text":2265,"url":24,"identifiers":2266},"Qi, X. et al. p38α antagonizes p38γ activity through c-Jun-dependent ubiquitin–proteasome pathways in regulating Ras transformation and stress response. J. Biol. Chem. 282, 31398–31408 (2007).",{"doi":2267},"10.1074\u002Fjbc.M703857200",{"id":24,"text":2269,"url":24,"identifiers":2270},"Alonso, G., Ambrosino, C., Jones, M. & Nebreda, A. R. Differential activation of p38 mitogen-activated protein kinase isoforms depending on signal strength. J. Biol. Chem. 275, 40641–40648 (2000).",{"doi":2271},"10.1074\u002Fjbc.M007835200",{"id":24,"text":2273,"url":24,"identifiers":2274},"Ge, B. et al. MAPKK-independent activation of p38α mediated by TAB1-dependent autophosphorylation of p38α. Science 295, 1291–1294 (2002). This paper presents evidence for a non-canonical mechanism of p38α activation based on TAB1-induced autophosphorylation.",{"doi":2275},"10.1126\u002Fscience.1067289",{"id":24,"text":2277,"url":24,"identifiers":2278},"Tanno, M. et al. Diverse mechanisms of myocardial p38 mitogen-activated protein kinase activation: evidence for MKK-independent activation by a TAB1-associated mechanism contributing to injury during myocardial ischemia. Circ. Res. 93, 254–261 (2003).",{"doi":2279},"10.1161\u002F01.RES.0000083490.43943.85",{"id":24,"text":2281,"url":24,"identifiers":2282},"DeNicola, G. F. et al. Mechanism and consequence of the autoactivation of p38α mitogen-activated protein kinase promoted by TAB1. Nat. Struct. Mol. Biol. 20, 1182–1190 (2013). This paper provides important structural information on the mechanism by which TAB1 binding triggers p38α autophosphorylation.",{"doi":2283},"10.1038\u002Fnsmb.2668",{"id":24,"text":2285,"url":24,"identifiers":2286},"De Nicola, G. F. et al. The TAB1–p38α complex aggravates myocardial injury and can be targeted by small molecules. JCI Insight 3, e121144 (2018).",{"doi":2287},"10.1172\u002Fjci.insight.121144",{"id":24,"text":2289,"url":24,"identifiers":2290},"Lanna, A., Henson, S. M., Escors, D. & Akbar, A. N. The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells. Nat. Immunol. 15, 965–972 (2014).",{"doi":2291},"10.1038\u002Fni.2981",{"id":24,"text":2293,"url":24,"identifiers":2294},"Theivanthiran, B. et al. The E3 ubiquitin ligase Itch inhibits p38α signaling and skin inflammation through the ubiquitylation of Tab1. Sci. Signal. 8, ra22 (2015).",{"doi":2295},"10.1126\u002Fscisignal.2005903",{"id":24,"text":2297,"url":24,"identifiers":2298},"Matesanz, N. et al. MKK6 controls T3-mediated browning of white adipose tissue. Nat. Commun. 8, 856 (2017).",{"doi":2299},"10.1038\u002Fs41467-017-00948-z",{"id":24,"text":2301,"url":24,"identifiers":2302},"Grimsey, N. J. et al. G protein-coupled receptors activate p38 MAPK via a non-canonical TAB1–TAB2- and TAB1–TAB3-dependent pathway in endothelial cells. J. Biol. Chem. 294, 5867–5878 (2019).",{"doi":2303},"10.1074\u002Fjbc.RA119.007495",{"id":24,"text":2305,"url":24,"identifiers":2306},"Salvador, J. M. et al. Alternative p38 activation pathway mediated by T cell receptor-proximal tyrosine kinases. Nat. Immunol. 6, 390–395 (2005). This paper describes an alternative mechanism of p38α activation that involves tyrosine phosphorylation and is specific for T cells.",{"doi":2307},"10.1038\u002Fni1177",{"id":24,"text":2309,"url":24,"identifiers":2310},"Mittelstadt, P. R., Yamaguchi, H., Appella, E. & Ashwell, J. D. T cell receptor-mediated activation of p38α by mono-phosphorylation of the activation loop results in altered substrate specificity. J. Biol. Chem. 284, 15469–15474 (2009).",{"doi":2311},"10.1074\u002Fjbc.M901004200",{"id":24,"text":2313,"url":24,"identifiers":2314},"Tomida, T., Takekawa, M. & Saito, H. Oscillation of p38 activity controls efficient pro-inflammatory gene expression. Nat. Commun. 6, 8350 (2015).",{"doi":2315},"10.1038\u002Fncomms9350",{"id":24,"text":2317,"url":24,"identifiers":2318},"Staples, C. J., Owens, D. M., Maier, J. V., Cato, A. C. & Keyse, S. M. Cross-talk between the p38α and JNK MAPK pathways mediated by MAP kinase phosphatase-1 determines cellular sensitivity to UV radiation. J. Biol. Chem. 285, 25928–25940 (2010).",{"doi":2319},"10.1074\u002Fjbc.M110.117911",{"id":24,"text":2321,"url":24,"identifiers":2322},"Miura, H., Kondo, Y., Matsuda, M. & Aoki, K. Cell-to-cell heterogeneity in p38-mediated cross-inhibition of JNK causes stochastic cell death. Cell Rep. 24, 2658–2668 (2018).",{"doi":2323},"10.1016\u002Fj.celrep.2018.08.020",{"id":24,"text":2325,"url":24,"identifiers":2326},"Ambrosino, C. et al. Negative feedback regulation of MKK6 mRNA stability by p38α mitogen-activated protein kinase. Mol. Cell Biol. 23, 370–381 (2003).",{"doi":2327},"10.1128\u002FMCB.23.1.370-381.2003",{"id":24,"text":2329,"url":24,"identifiers":2330},"Cheung, P. C., Campbell, D. G., Nebreda, A. R. & Cohen, P. Feedback control of the protein kinase TAK1 by SAPK2a\u002Fp38α. EMBO J. 22, 5793–5805 (2003).",{"doi":2331},"10.1093\u002Femboj\u002Fcdg552",{"id":24,"text":2333,"url":24,"identifiers":2334},"Giardino Torchia, M. L. et al. Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70T293 and destabilization of the signalosome. Proc. Natl Acad. Sci. USA 115, 2174–2179 (2018).",{"doi":2335},"10.1073\u002Fpnas.1713301115",{"id":24,"text":2337,"url":24,"identifiers":2338},"Peregrin, S. et al. Phosphorylation of p38 by GRK2 at the docking groove unveils a novel mechanism for inactivating p38MAPK. Curr. Biol. 16, 2042–2047 (2006).",{"doi":2339},"10.1016\u002Fj.cub.2006.08.083",{"id":24,"text":2341,"url":24,"identifiers":2342},"Salvador, J. M., Mittelstadt, P. R., Belova, G. I., Fornace, A. J. Jr. & Ashwell, J. D. The autoimmune suppressor Gadd45α inhibits the T cell alternative p38 activation pathway. Nat. Immunol. 6, 396–402 (2005).",{"doi":2343},"10.1038\u002Fni1176",{"id":24,"text":2345,"url":24,"identifiers":2346},"Wu, Y. H. et al. Tumor suppressor death-associated protein kinase 1 inhibits necroptosis by p38 MAPK activation. Cell Death Dis. 11, 305 (2020).",{"doi":2347},"10.1038\u002Fs41419-020-2534-9",{"id":24,"text":2349,"url":24,"identifiers":2350},"Pillai, V. B. et al. Acetylation of a conserved lysine residue in the ATP binding pocket of p38 augments its kinase activity during hypertrophy of cardiomyocytes. Mol. Cell Biol. 31, 2349–2363 (2011).",{"doi":2351},"10.1128\u002FMCB.01205-10",{"id":24,"text":2353,"url":24,"identifiers":2354},"Brichkina, A. et al. Proline isomerisation as a novel regulatory mechanism for p38MAPK activation and functions. Cell Death Differ. 23, 1592–1601 (2016).",{"doi":2355},"10.1038\u002Fcdd.2016.45",{"id":24,"text":2357,"url":24,"identifiers":2358},"Jeong, H. J. et al. Prmt7 promotes myoblast differentiation via methylation of p38MAPK on arginine residue 70. Cell Death Differ. 27, 573–586 (2020).",{"doi":2359},"10.1038\u002Fs41418-019-0373-y",{"id":24,"text":2361,"url":24,"identifiers":2362},"Liu, M. Y., Hua, W. K., Chen, C. J. & Lin, W. J. The MKK-dependent phosphorylation of p38α is augmented by arginine methylation on Arg49\u002FArg149 during erythroid differentiation. Int. J. Mol. Sci. 21, 3546 (2020).",{"doi":2363},"10.3390\u002Fijms21103546",{"id":24,"text":2365,"url":24,"identifiers":2366},"Round, J. L. et al. Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-κB transcription factors. Nat. Immunol. 8, 154–161 (2007).",{"doi":2367},"10.1038\u002Fni1422",{"id":24,"text":2369,"url":24,"identifiers":2370},"Uhlik, M. T. et al. Rac–MEKK3–MKK3 scaffolding for p38 MAPK activation during hyperosmotic shock. Nat. Cell Biol. 5, 1104–1110 (2003).",{"doi":2371},"10.1038\u002Fncb1071",{"id":24,"text":2373,"url":24,"identifiers":2374},"Zehorai, E. & Seger, R. Beta-like importins mediate the nuclear translocation of mitogen-activated protein kinases. Mol. Cell Biol. 34, 259–270 (2014).",{"doi":2375},"10.1128\u002FMCB.00799-13",{"id":24,"text":2377,"url":24,"identifiers":2378},"Weaver, B. P. et al. Non-canonical caspase activity antagonizes p38 MAPK stress-priming function to support development. Dev. Cell 53, 358–369.e6 (2020).",{"doi":2379},"10.1016\u002Fj.devcel.2020.03.015",{"id":24,"text":2381,"url":24,"identifiers":2382},"Liu, K. et al. Mutual stabilization between TRIM9 short isoform and MKK6 potentiates p38 signaling to synergistically suppress glioblastoma progression. Cell Rep. 23, 838–851 (2018).",{"doi":2383},"10.1016\u002Fj.celrep.2018.03.096",{"id":24,"text":2385,"url":24,"identifiers":2386},"Liu, J. et al. F-box only protein 31 (FBXO31) negatively regulates p38 mitogen-activated protein kinase (MAPK) signaling by mediating lysine 48-linked ubiquitination and degradation of mitogen-activated protein kinase kinase 6 (MKK6). J. Biol. Chem. 289, 21508–21518 (2014).",{"doi":2387},"10.1074\u002Fjbc.M114.560342",{"id":24,"text":2389,"url":24,"identifiers":2390},"Zou, X. & Blank, M. Targeting p38 MAP kinase signaling in cancer through post-translational modifications. Cancer Lett. 384, 19–26 (2017).",{"doi":2391},"10.1016\u002Fj.canlet.2016.10.008",{"id":24,"text":2393,"url":24,"identifiers":2394},"Diao, Y. et al. Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding. Proc. Natl Acad. Sci. USA 107, 20974–20979 (2010).",{"doi":2395},"10.1073\u002Fpnas.1007225107",{"id":24,"text":2397,"url":24,"identifiers":2398},"Rasmussen, M. H. et al. miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells. Nat. Commun. 7, 12436 (2016).",{"doi":2399},"10.1038\u002Fncomms12436",{"id":24,"text":2401,"url":24,"identifiers":2402},"Turk, B. E. Manipulation of host signalling pathways by anthrax toxins. Biochem. J. 402, 405–417 (2007).",{"doi":2403},"10.1042\u002FBJ20061891",{"id":24,"text":2405,"url":24,"identifiers":2406},"Mukherjee, S. et al. Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation. Science 312, 1211–1214 (2006).",{"doi":2407},"10.1126\u002Fscience.1126867",{"id":24,"text":2409,"url":24,"identifiers":2410},"Paquette, N. et al. Serine\u002Fthreonine acetylation of TGFβ-activated kinase (TAK1) by Yersinia pestis YopJ inhibits innate immune signaling. Proc. Natl Acad. Sci. USA 109, 12710–12715 (2012).",{"doi":2411},"10.1073\u002Fpnas.1008203109",{"id":24,"text":2413,"url":24,"identifiers":2414},"Pellegrini, E. et al. Structural basis for the subversion of MAP kinase signaling by an intrinsically disordered parasite secreted agonist. Structure 25, 16–26 (2017).",{"doi":2415},"10.1016\u002Fj.str.2016.10.011",{"id":24,"text":2417,"url":24,"identifiers":2418},"Katz, M., Amit, I. & Yarden, Y. Regulation of MAPKs by growth factors and receptor tyrosine kinases. Biochim. Biophys. Acta 1773, 1161–1176 (2007).",{"doi":2419},"10.1016\u002Fj.bbamcr.2007.01.002",{"id":24,"text":2421,"url":24,"identifiers":2422},"Faust, D. et al. Differential p38-dependent signalling in response to cellular stress and mitogenic stimulation in fibroblasts. Cell Commun. Signal. 10, 6 (2012).",{"doi":2423},"10.1186\u002F1478-811X-10-6",{"id":24,"text":2425,"url":24,"identifiers":2426},"Sakauchi, C., Wakatsuki, H., Ichijo, H. & Hattori, K. Pleiotropic properties of ASK1. Biochim. Biophys. Acta Gen. Subj. 1861, 3030–3038 (2017).",{"doi":2427},"10.1016\u002Fj.bbagen.2016.09.028",{"id":24,"text":2429,"url":24,"identifiers":2430},"Matsushita, M., Nakamura, T., Moriizumi, H., Miki, H. & Takekawa, M. Stress-responsive MTK1 SAPKKK serves as a redox sensor that mediates delayed and sustained activation of SAPKs by oxidative stress. Sci. Adv. 6, eaay9778 (2020).",{"doi":2431},"10.1126\u002Fsciadv.aay9778",{"id":24,"text":2433,"url":24,"identifiers":2434},"Dolado, I. et al. p38α MAP kinase as a sensor of reactive oxygen species in tumorigenesis. Cancer Cell 11, 191–205 (2007).",{"doi":2435},"10.1016\u002Fj.ccr.2006.12.013",{"id":24,"text":2437,"url":24,"identifiers":2438},"Coelho, M. A. et al. Oncogenic RAS signaling promotes tumor immunoresistance by stabilizing PD-L1 mRNA. Immunity 47, 1083–1099.e6 (2017).",{"doi":2439},"10.1016\u002Fj.immuni.2017.11.016",{"id":24,"text":2441,"url":24,"identifiers":2442},"Rodriguez-Colman, M. J. et al. Interplay between metabolic identities in the intestinal crypt supports stem cell function. Nature 543, 424–427 (2017). This article shows that physiological levels of ROS produced by mitochondrial OXPHOS activate p38α in intestinal stem cells to ensure intestinal crypt homeostasis.",{"doi":2443},"10.1038\u002Fnature21673",{"id":24,"text":2445,"url":24,"identifiers":2446},"L’Honore, A. et al. The role of Pitx2 and Pitx3 in muscle stem cells gives new insights into p38α MAP kinase and redox regulation of muscle regeneration. eLife 7, e32991 (2018).",{"doi":2447},"10.7554\u002FeLife.32991",{"id":24,"text":2449,"url":24,"identifiers":2450},"Fukawa, T. et al. Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia. Nat. Med. 22, 666–671 (2016).",{"doi":2451},"10.1038\u002Fnm.4093",{"id":24,"text":2453,"url":24,"identifiers":2454},"Cheng, C. T. et al. Metabolic stress-induced phosphorylation of KAP1 Ser473 blocks mitochondrial fusion in breast cancer cells. Cancer Res. 76, 5006–5018 (2016).",{"doi":2455},"10.1158\u002F0008-5472.CAN-15-2921",{"id":24,"text":2457,"url":24,"identifiers":2458},"Geller, S. et al. Tanycytes regulate lipid homeostasis by sensing free fatty acids and signaling to key hypothalamic neuronal populations via FGF21 secretion. Cell Metab. 30, 833–844.e7 (2019).",{"doi":2459},"10.1016\u002Fj.cmet.2019.08.004",{"id":24,"text":2461,"url":24,"identifiers":2462},"Sabio, G. & Davis, R. J. TNF and MAP kinase signalling pathways. Semin. Immunol. 26, 237–245 (2014).",{"doi":2463},"10.1016\u002Fj.smim.2014.02.009",{"id":24,"text":2465,"url":24,"identifiers":2466},"Lin, J., Lee, D., Choi, Y. & Lee, S. Y. The scaffold protein RACK1 mediates the RANKL-dependent activation of p38 MAPK in osteoclast precursors. Sci. Signal. 8, ra54 (2015).",{"doi":2467},"10.1126\u002Fscisignal.2005867",{"id":24,"text":2469,"url":24,"identifiers":2470},"Tzavlaki, K. & Moustakas, A. TGF-β signaling. Biomolecules 10, 487 (2020).",{"doi":2471},"10.3390\u002Fbiom10030487",{"id":24,"text":2473,"url":24,"identifiers":2474},"Sapkota, G. P. The TGFβ-induced phosphorylation and activation of p38 mitogen-activated protein kinase is mediated by MAP3K4 and MAP3K10 but not TAK1. Open. Biol. 3, 130067 (2013).",{"doi":2475},"10.1098\u002Frsob.130067",{"id":24,"text":2477,"url":24,"identifiers":2478},"Gaestel, M., Kotlyarov, A. & Kracht, M. Targeting innate immunity protein kinase signalling in inflammation. Nat. Rev. Drug Discov. 8, 480–499 (2009).",{"doi":2479},"10.1038\u002Fnrd2829",{"id":24,"text":2481,"url":24,"identifiers":2482},"Arthur, J. S. & Ley, S. C. Mitogen-activated protein kinases in innate immunity. Nat. Rev. Immunol. 13, 679–692 (2013).",{"doi":2483},"10.1038\u002Fnri3495",{"id":24,"text":2485,"url":24,"identifiers":2486},"Takizawa, H. et al. Pathogen-induced TLR4–TRIF innate immune signaling in hematopoietic stem cells promotes proliferation but reduces competitive fitness. Cell Stem Cell 21, 225–240.e5 (2017).",{"doi":2487},"10.1016\u002Fj.stem.2017.06.013",{"id":24,"text":2489,"url":24,"identifiers":2490},"Lee, W. B. et al. Mincle-mediated translational regulation is required for strong nitric oxide production and inflammation resolution. Nat. Commun. 7, 11322 (2016).",{"doi":2491},"10.1038\u002Fncomms11322",{"id":24,"text":2493,"url":24,"identifiers":2494},"Johnson, R. A., Huong, S. M. & Huang, E. S. Activation of the mitogen-activated protein kinase p38 by human cytomegalovirus infection through two distinct pathways: a novel mechanism for activation of p38. J. Virol. 74, 1158–1167 (2000).",{"doi":2495},"10.1128\u002FJVI.74.3.1158-1167.2000",{"id":24,"text":2497,"url":24,"identifiers":2498},"Bouhaddou, M. et al. The global phosphorylation landscape of SARS-CoV-2 infection. Cell 182, 685–712.e19 (2020).",{"doi":2499},"10.1016\u002Fj.cell.2020.06.034",{"id":24,"text":2501,"url":24,"identifiers":2502},"Wagstaff, L. et al. Mechanical cell competition kills cells via induction of lethal p53 levels. Nat. Commun. 7, 11373 (2016).",{"doi":2503},"10.1038\u002Fncomms11373",{"id":24,"text":2505,"url":24,"identifiers":2506},"Hofmann, M. et al. Mechanical pressure-induced phosphorylation of p38 mitogen-activated protein kinase in epithelial cells via Src and protein kinase C. Biochem. Biophys. Res. Commun. 316, 673–679 (2004).",{"doi":2507},"10.1016\u002Fj.bbrc.2004.02.101",{"id":24,"text":2509,"url":24,"identifiers":2510},"Liu, Z. et al. MAPK-mediated YAP activation controls mechanical-tension-induced pulmonary alveolar regeneration. Cell Rep. 16, 1810–1819 (2016).",{"doi":2511},"10.1016\u002Fj.celrep.2016.07.020",{"id":24,"text":2513,"url":24,"identifiers":2514},"Raman, M., Earnest, S., Zhang, K., Zhao, Y. & Cobb, M. H. TAO kinases mediate activation of p38 in response to DNA damage. EMBO J. 26, 2005–2014 (2007).",{"doi":2515},"10.1038\u002Fsj.emboj.7601668",{"id":24,"text":2517,"url":24,"identifiers":2518},"Colomer, C. et al. IKKα kinase regulates the DNA damage response and drives chemo-resistance in cancer. Mol. Cell 75, 669–682.e5 (2019).",{"doi":2519},"10.1016\u002Fj.molcel.2019.05.036",{"id":24,"text":2521,"url":24,"identifiers":2522},"Bent, E. H., Gilbert, L. A. & Hemann, M. T. A senescence secretory switch mediated by PI3K\u002FAKT\u002FmTOR activation controls chemoprotective endothelial secretory responses. Genes Dev. 30, 1811–1821 (2016).",{"doi":2523},"10.1101\u002Fgad.284851.116",{"id":24,"text":2525,"url":24,"identifiers":2526},"Lu, H. et al. Reciprocal regulation of DUSP9 and DUSP16 expression by HIF1 controls ERK and p38 MAP kinase activity and mediates chemotherapy-induced breast cancer stem cell enrichment. Cancer Res. 78, 4191–4202 (2018).",{"doi":2527},"10.1158\u002F0008-5472.CAN-18-0270",{"id":24,"text":2529,"url":24,"identifiers":2530},"Trempolec, N., Dave-Coll, N. & Nebreda, A. R. SnapShot: p38 MAPK substrates. Cell 152, 924–924.e1 (2013).",{"doi":2531},"10.1016\u002Fj.cell.2013.01.047",{"id":24,"text":2533,"url":24,"identifiers":2534},"Gaestel, M. MAPK-activated protein kinases (MKs): novel insights and challenges. Front. Cell Dev. Biol. 3, 88 (2015).",{},{"id":24,"text":2536,"url":24,"identifiers":2537},"Reyskens, K. M. & Arthur, J. S. Emerging roles of the mitogen and stress activated kinases MSK1 and MSK2. Front. Cell Dev. Biol. 4, 56 (2016).",{"doi":2538},"10.3389\u002Ffcell.2016.00056",{"id":24,"text":2540,"url":24,"identifiers":2541},"Joshi, S. & Platanias, L. C. Mnk kinase pathway: cellular functions and biological outcomes. World J. Biol. Chem. 5, 321–333 (2014).",{"doi":2542},"10.4331\u002Fwjbc.v5.i3.321",{"id":24,"text":2544,"url":24,"identifiers":2545},"Dolado, I. & Nebreda, A. R. Regulation of tumorigenesis by p38α MAP kinase. Top. Curr. 20, 99–128 (2008).",{},{"id":24,"text":2547,"url":24,"identifiers":2548},"Cannell, I. G. et al. A pleiotropic RNA-binding protein controls distinct cell cycle checkpoints to drive resistance of p53-defective tumors to chemotherapy. Cancer Cell 28, 623–637 (2015).",{"doi":2549},"10.1016\u002Fj.ccell.2015.09.009",{"id":24,"text":2551,"url":24,"identifiers":2552},"Gubern, A. et al. The N-terminal phosphorylation of RB by p38 bypasses its inactivation by CDKs and prevents proliferation in cancer cells. Mol. Cell 64, 25–36 (2016).",{"doi":2553},"10.1016\u002Fj.molcel.2016.08.015",{"id":24,"text":2555,"url":24,"identifiers":2556},"Muranen, T. et al. ERK and p38 MAPK activities determine sensitivity to PI3K\u002FmTOR inhibition via regulation of MYC and YAP. Cancer Res. 76, 7168–7180 (2016).",{"doi":2557},"10.1158\u002F0008-5472.CAN-16-0155",{"id":24,"text":2559,"url":24,"identifiers":2560},"Phong, M. S. et al. p38 mitogen-activated protein kinase promotes cell survival in response to DNA damage but is not required for the G2 DNA damage checkpoint in human cancer cells. Mol. Cell Biol. 30, 3816–3826 (2010).",{"doi":2561},"10.1128\u002FMCB.00949-09",{"id":24,"text":2563,"url":24,"identifiers":2564},"Guil, S., Long, J. C. & Caceres, J. F. hnRNP A1 relocalization to the stress granules reflects a role in the stress response. Mol. Cell Biol. 26, 5744–5758 (2006).",{"doi":2565},"10.1128\u002FMCB.00224-06",{"id":24,"text":2567,"url":24,"identifiers":2568},"Carbonell, C. et al. Functional network analysis reveals the relevance of SKIIP in the regulation of alternative splicing by p38 SAPK. Cell Rep. 27, 847–859.e6 (2019).",{"doi":2569},"10.1016\u002Fj.celrep.2019.03.060",{"id":24,"text":2571,"url":24,"identifiers":2572},"Borisova, M. E. et al. p38–MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage. Nat. Commun. 9, 1017 (2018).",{"doi":2573},"10.1038\u002Fs41467-018-03417-3",{"id":24,"text":2575,"url":24,"identifiers":2576},"Bugai, A. et al. P-TEFb activation by RBM7 shapes a pro-survival transcriptional response to genotoxic stress. Mol. Cell 74, 254–267.e10 (2019).",{"doi":2577},"10.1016\u002Fj.molcel.2019.01.033",{"id":24,"text":2579,"url":24,"identifiers":2580},"Li, W. et al. Phosphorylation of LAMP2A by p38 MAPK couples ER stress to chaperone-mediated autophagy. Nat. Commun. 8, 1763 (2017).",{"doi":2581},"10.1038\u002Fs41467-017-01609-x",{"id":24,"text":2583,"url":24,"identifiers":2584},"Wei, Y. et al. The stress-responsive kinases MAPKAPK2\u002FMAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation. eLife 4, e05289 (2015).",{"doi":2585},"10.7554\u002FeLife.05289",{"id":24,"text":2587,"url":24,"identifiers":2588},"Slobodnyuk, K. et al. Autophagy-induced senescence is regulated by p38α signaling. Cell Death Dis. 10, 376 (2019).",{"doi":2589},"10.1038\u002Fs41419-019-1607-0",{"id":24,"text":2591,"url":24,"identifiers":2592},"Hwang, S. et al. Protective and detrimental roles of p38α MAPK in different stages of nonalcoholic fatty liver disease. Hepatology 72, 873–891 (2020).",{"doi":2593},"10.1002\u002Fhep.31390",{"id":24,"text":2595,"url":24,"identifiers":2596},"Soustek, M. S. et al. Inhibition of the ER stress IRE1α inflammatory pathway protects against cell death in mitochondrial complex I mutant cells. Cell Death Dis. 9, 658 (2018).",{"doi":2597},"10.1038\u002Fs41419-018-0696-5",{"id":24,"text":2599,"url":24,"identifiers":2600},"Yang, Q. et al. Stress induces p38 MAPK-mediated phosphorylation and inhibition of Drosha-dependent cell survival. Mol. Cell 57, 721–734 (2015).",{"doi":2601},"10.1016\u002Fj.molcel.2015.01.004",{"id":24,"text":2603,"url":24,"identifiers":2604},"Lin, K. C. et al. Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation. Nat. Cell Biol. 19, 996–1002 (2017).",{"doi":2605},"10.1038\u002Fncb3581",{"id":24,"text":2607,"url":24,"identifiers":2608},"Trempolec, N. et al. Induction of oxidative metabolism by the p38α\u002FMK2 pathway. Sci. Rep. 7, 11367 (2017).",{"doi":2609},"10.1038\u002Fs41598-017-11309-7",{"id":24,"text":2611,"url":24,"identifiers":2612},"Leestemaker, Y. et al. Proteasome activation by small molecules. Cell Chem. Biol. 24, 725–736.e7 (2017).",{"doi":2613},"10.1016\u002Fj.chembiol.2017.05.010",{"id":24,"text":2615,"url":24,"identifiers":2616},"Simoes-Sousa, S. et al. The p38α stress kinase suppresses aneuploidy tolerance by inhibiting Hif-1α. Cell Rep. 25, 749–760.e6 (2018).",{"doi":2617},"10.1016\u002Fj.celrep.2018.09.060",{"id":24,"text":2619,"url":24,"identifiers":2620},"Canovas, B. et al. Targeting p38α increases DNA damage, chromosome instability, and the anti-tumoral response to taxanes in breast cancer cells. Cancer Cell 33, 1094–1110.e8 (2018). This paper describes a p38α-mediated mechanism that regulates DNA repair in cancer cells, and provides evidence that pharmacological inhibitors of p38α potentiate the cytotoxic effect of taxanes in breast cancer mouse models and patient-derived xenografts.",{"doi":2621},"10.1016\u002Fj.ccell.2018.04.010",{"id":24,"text":2623,"url":24,"identifiers":2624},"Herbert, K. et al. BRN2 suppresses apoptosis, reprograms DNA damage repair, and is associated with a high somatic mutation burden in melanoma. Genes Dev. 33, 310–332 (2019).",{"doi":2625},"10.1101\u002Fgad.314633.118",{"id":24,"text":2627,"url":24,"identifiers":2628},"Kang, Y. J. et al. Macrophage deletion of p38α partially impairs lipopolysaccharide-induced cellular activation. J. Immunol. 180, 5075–5082 (2008).",{"doi":2629},"10.4049\u002Fjimmunol.180.7.5075",{"id":24,"text":2631,"url":24,"identifiers":2632},"Youssif, C. et al. Myeloid p38α signaling promotes intestinal IGF-1 production and inflammation-associated tumorigenesis. EMBO Mol. Med. 10, e8403 (2018).",{"doi":2633},"10.15252\u002Femmm.201708403",{"id":24,"text":2635,"url":24,"identifiers":2636},"Zheng, T. et al. Protein kinase p38α signaling in dendritic cells regulates colon inflammation and tumorigenesis. Proc. Natl Acad. Sci. USA 115, E12313–E12322 (2018).",{"doi":2637},"10.1073\u002Fpnas.1814705115",{"id":24,"text":2639,"url":24,"identifiers":2640},"Li, C. et al. Dendritic cell MST1 inhibits TH17 differentiation. Nat. Commun. 8, 14275 (2017).",{"doi":2641},"10.1038\u002Fncomms14275",{"id":24,"text":2643,"url":24,"identifiers":2644},"Li, J. et al. Activation of DR3 signaling causes loss of ILC3s and exacerbates intestinal inflammation. Nat. Commun. 10, 3371 (2019).",{"doi":2645},"10.1038\u002Fs41467-019-11304-8",{"id":24,"text":2647,"url":24,"identifiers":2648},"Petrova, T., Pesic, J., Pardali, K., Gaestel, M. & Arthur, J. S. C. p38 MAPK signalling regulates cytokine production in IL-33 stimulated type 2 innate lymphoid cells. Sci. Rep. 10, 3479 (2020).",{"doi":2649},"10.1038\u002Fs41598-020-60089-0",{"id":24,"text":2651,"url":24,"identifiers":2652},"Gopfert, C. et al. The p38-MK2\u002F3 module is critical for IL-33-induced signaling and cytokine production in dendritic cells. J. Immunol. 200, 1198–1206 (2018).",{"doi":2653},"10.4049\u002Fjimmunol.1700727",{"id":24,"text":2655,"url":24,"identifiers":2656},"McCarthy, P. C. et al. IL-33 regulates cytokine production and neutrophil recruitment via the p38 MAPK-activated kinases MK2\u002F3. Immunol. Cell Biol. 97, 54–71 (2019).",{"doi":2657},"10.1111\u002Fimcb.12200",{"id":24,"text":2659,"url":24,"identifiers":2660},"Bhattacharya, S. et al. Role of p38 protein kinase in the ligand-independent ubiquitination and down-regulation of the IFNAR1 chain of type I interferon receptor. J. Biol. Chem. 286, 22069–22076 (2011).",{"doi":2661},"10.1074\u002Fjbc.M111.238766",{"id":24,"text":2663,"url":24,"identifiers":2664},"Fuchs, S. Y. Ubiquitination-mediated regulation of interferon responses. Growth Factors 30, 141–148 (2012).",{"doi":2665},"10.3109\u002F08977194.2012.669382",{"id":24,"text":2667,"url":24,"identifiers":2668},"Katlinski, K. V. et al. Inactivation of interferon receptor promotes the establishment of immune privileged tumor microenvironment. Cancer Cell 31, 194–207 (2017).",{"doi":2669},"10.1016\u002Fj.ccell.2017.01.004",{"id":24,"text":2671,"url":24,"identifiers":2672},"Ortiz, A. et al. An interferon-driven oxysterol-based defense against tumor-derived extracellular vesicles. Cancer Cell 35, 33–45.e6 (2019).",{"doi":2673},"10.1016\u002Fj.ccell.2018.12.001",{"id":24,"text":2675,"url":24,"identifiers":2676},"Gui, J. et al. Activation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs. Nat. Cancer 1, 603–619 (2020). This extensive study analyses how p38α signalling in fibroblasts facilitates lung tumour growth.",{"doi":2677},"10.1038\u002Fs43018-020-0064-0",{"id":24,"text":2679,"url":24,"identifiers":2680},"De Maeyer, R. P. H. et al. Blocking elevated p38 MAPK restores efferocytosis and inflammatory resolution in the elderly. Nat. Immunol. 21, 615–625 (2020). This paper shows that pharmacological inhibition of p38α restores the macrophage-mediated resolution of dermal inflammation in older humans, supporting that p38α inhibitors might be useful to treat particular inflammatory diseases.",{"doi":2681},"10.1038\u002Fs41590-020-0646-0",{"id":24,"text":2683,"url":24,"identifiers":2684},"Jaco, I. et al. MK2 phosphorylates RIPK1 to prevent TNF-induced cell death. Mol. Cell 66, 698–710.e5 (2017).",{"doi":2685},"10.1016\u002Fj.molcel.2017.05.003",{"id":24,"text":2687,"url":24,"identifiers":2688},"Dondelinger, Y. et al. MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death. Nat. Cell Biol. 19, 1237–1247 (2017).",{"doi":2689},"10.1038\u002Fncb3608",{"id":24,"text":2691,"url":24,"identifiers":2692},"Menon, M. B. et al. p38MAPK\u002FMK2-dependent phosphorylation controls cytotoxic RIPK1 signalling in inflammation and infection. Nat. Cell Biol. 19, 1248–1259 (2017). Together with Jaco et al. (2017) and Dondelinger et al. (2017), this paper demonstrates an important role for the p38\u002FMK2 pathway restraining TNF-induced cell death through the phosphorylation of RIPK1.",{"doi":2693},"10.1038\u002Fncb3614",{"id":24,"text":2695,"url":24,"identifiers":2696},"Segales, J., Perdiguero, E. & Munoz-Canoves, P. Regulation of muscle stem cell functions: a focus on the p38 MAPK signaling pathway. Front. Cell Dev. Biol. 4, 91 (2016).",{"doi":2697},"10.3389\u002Ffcell.2016.00091",{"id":24,"text":2699,"url":24,"identifiers":2700},"Consalvi, S., Brancaccio, A., Dall’Agnese, A., Puri, P. L. & Palacios, D. Praja1 E3 ubiquitin ligase promotes skeletal myogenesis through degradation of EZH2 upon p38α activation. Nat. Commun. 8, 13956 (2017).",{"doi":2701},"10.1038\u002Fncomms13956",{"id":24,"text":2703,"url":24,"identifiers":2704},"Rodriguez-Carballo, E., Gamez, B. & Ventura, F. p38 MAPK signaling in osteoblast differentiation. Front. Cell Dev. Biol. 4, 40 (2016).",{"doi":2705},"10.3389\u002Ffcell.2016.00040",{"id":24,"text":2707,"url":24,"identifiers":2708},"Bost, F., Aouadi, M., Caron, L. & Binetruy, B. The role of MAPKs in adipocyte differentiation and obesity. Biochimie 87, 51–56 (2005).",{"doi":2709},"10.1016\u002Fj.biochi.2004.10.018",{"id":24,"text":2711,"url":24,"identifiers":2712},"Cao, W. et al. p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol. Cell Biol. 24, 3057–3067 (2004). This paper describes p38 kinase signalling as a central regulator of thermogenesis in brown adipocytes.",{"doi":2713},"10.1128\u002FMCB.24.7.3057-3067.2004",{"id":24,"text":2715,"url":24,"identifiers":2716},"Hattori, K. et al. ASK1 signalling regulates brown and beige adipocyte function. Nat. Commun. 7, 11158 (2016).",{"doi":2717},"10.1038\u002Fncomms11158",{"id":24,"text":2719,"url":24,"identifiers":2720},"Yi, D. et al. Zc3h10 acts as a transcription factor and is phosphorylated to activate the thermogenic program. Cell Rep. 29, 2621–2633.e4 (2019).",{"doi":2721},"10.1016\u002Fj.celrep.2019.10.099",{"id":24,"text":2723,"url":24,"identifiers":2724},"Ng, R. et al. miRNA-32 drives brown fat thermogenesis and trans-activates subcutaneous white fat browning in mice. Cell Rep. 19, 1229–1246 (2017).",{"doi":2725},"10.1016\u002Fj.celrep.2017.04.035",{"id":24,"text":2727,"url":24,"identifiers":2728},"Quesada-Lopez, T. et al. The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes. Nat. Commun. 7, 13479 (2016).",{"doi":2729},"10.1038\u002Fncomms13479",{"id":24,"text":2731,"url":24,"identifiers":2732},"Hu, P. et al. p38α\u002FJNK signaling restrains erythropoiesis by suppressing Ezh2-mediated epigenetic silencing of Bim. Nat. Commun. 9, 3518 (2018).",{"doi":2733},"10.1038\u002Fs41467-018-05955-2",{"id":24,"text":2735,"url":24,"identifiers":2736},"Batlle, R. et al. Regulation of tumor angiogenesis and mesenchymal–endothelial transition by p38α through TGF-β and JNK signaling. Nat. Commun. 10, 3071 (2019).",{"doi":2737},"10.1038\u002Fs41467-019-10946-y",{"id":24,"text":2739,"url":24,"identifiers":2740},"Oeztuerk-Winder, F. & Ventura, J. J. The many faces of p38 mitogen-activated protein kinase in progenitor\u002Fstem cell differentiation. Biochem. J. 445, 1–10 (2012).",{"doi":2741},"10.1042\u002FBJ20120401",{"id":24,"text":2743,"url":24,"identifiers":2744},"Wu, X. et al. CUG-binding protein 1 regulates HSC activation and liver fibrogenesis. Nat. Commun. 7, 13498 (2016).",{"doi":2745},"10.1038\u002Fncomms13498",{"id":24,"text":2747,"url":24,"identifiers":2748},"Choo, M. K., Kraft, S., Missero, C. & Park, J. M. The protein kinase p38α destabilizes p63 to limit epidermal stem cell frequency and tumorigenic potential. Sci. Signal. 11, eaau0727 (2018).",{"doi":2749},"10.1126\u002Fscisignal.aau0727",{"id":24,"text":2751,"url":24,"identifiers":2752},"He, D. et al. Gut stem cell aging is driven by mTORC1 via a p38 MAPK–p53 pathway. Nat. Commun. 11, 37 (2020).",{"doi":2753},"10.1038\u002Fs41467-019-13911-x",{"id":24,"text":2755,"url":24,"identifiers":2756},"Karigane, D. et al. p38α activates purine metabolism to initiate hematopoietic stem\u002Fprogenitor cell cycling in response to stress. Cell Stem Cell 19, 192–204 (2016).",{"doi":2757},"10.1016\u002Fj.stem.2016.05.013",{"id":24,"text":2759,"url":24,"identifiers":2760},"Ito, K. et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat. Med. 12, 446–451 (2006).",{"doi":2761},"10.1038\u002Fnm1388",{"id":24,"text":2763,"url":24,"identifiers":2764},"Freund, A., Patil, C. K. & Campisi, J. p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype. EMBO J. 30, 1536–1548 (2011).",{"doi":2765},"10.1038\u002Femboj.2011.69",{"id":24,"text":2767,"url":24,"identifiers":2768},"Alspach, E. et al. p38MAPK plays a crucial role in stromal-mediated tumorigenesis. Cancer Discov. 4, 716–729 (2014).",{"doi":2769},"10.1158\u002F2159-8290.CD-13-0743",{"id":24,"text":2771,"url":24,"identifiers":2772},"Herranz, N. et al. mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype. Nat. Cell Biol. 17, 1205–1217 (2015).",{"doi":2773},"10.1038\u002Fncb3225",{"id":24,"text":2775,"url":24,"identifiers":2776},"Hu, J. H. et al. Activity-dependent isomerization of Kv4.2 by Pin1 regulates cognitive flexibility. Nat. Commun. 11, 1567 (2020).",{"doi":2777},"10.1038\u002Fs41467-020-15390-x",{"id":24,"text":2779,"url":24,"identifiers":2780},"Liu, K. et al. PI31 is an adaptor protein for proteasome transport in axons and required for synaptic development. Dev. Cell 50, 509–524.e10 (2019).",{"doi":2781},"10.1016\u002Fj.devcel.2019.06.009",{"id":24,"text":2783,"url":24,"identifiers":2784},"Lloret, A., Fuchsberger, T., Giraldo, E. & Vina, J. Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimers disease. Free Radic. Biol. Med. 83, 186–191 (2015).",{"doi":2785},"10.1016\u002Fj.freeradbiomed.2015.02.028",{"id":24,"text":2787,"url":24,"identifiers":2788},"Chen, J. et al. Phosphorylation of Parkin at serine 131 by p38 MAPK promotes mitochondrial dysfunction and neuronal death in mutant A53T α-synuclein model of Parkinson’s disease. Cell Death Dis. 9, 700 (2018).",{"doi":2789},"10.1038\u002Fs41419-018-0722-7",{"id":24,"text":2791,"url":24,"identifiers":2792},"Ashwell, J. D. The many paths to p38 mitogen-activated protein kinase activation in the immune system. Nat. Rev. Immunol. 6, 532–540 (2006).",{"doi":2793},"10.1038\u002Fnri1865",{"id":24,"text":2795,"url":24,"identifiers":2796},"Jun, J. E., Kulhanek, K. R., Chen, H., Chakraborty, A. & Roose, J. P. Alternative ZAP70–p38 signals prime a classical p38 pathway through LAT and SOS to support regulatory T cell differentiation. Sci. Signal. 12, eaao0736 (2019).",{"doi":2797},"10.1126\u002Fscisignal.aao0736",{"id":24,"text":2799,"url":24,"identifiers":2800},"Alam, M. S. et al. Counter-regulation of T cell effector function by differentially activated p38. J. Exp. Med. 211, 1257–1270 (2014).",{"doi":2801},"10.1084\u002Fjem.20131917",{"id":24,"text":2803,"url":24,"identifiers":2804},"Mace, G., Miaczynska, M., Zerial, M. & Nebreda, A. R. Phosphorylation of EEA1 by p38 MAP kinase regulates μ opioid receptor endocytosis. EMBO J. 24, 3235–3246 (2005).",{"doi":2805},"10.1038\u002Fsj.emboj.7600799",{"id":24,"text":2807,"url":24,"identifiers":2808},"Biondi, R. M. & Nebreda, A. R. Signalling specificity of Ser\u002FThr protein kinases through docking-site-mediated interactions. Biochem. J. 372, 1–13 (2003).",{"doi":2809},"10.1042\u002Fbj20021641",{"id":24,"text":2811,"url":24,"identifiers":2812},"Zeke, A. et al. Systematic discovery of linear binding motifs targeting an ancient protein interaction surface on MAP kinases. Mol. Syst. Biol. 11, 837 (2015).",{"doi":2813},"10.15252\u002Fmsb.20156269",{"id":24,"text":2815,"url":24,"identifiers":2816},"Jung, H. et al. Thioredoxin-interacting protein regulates haematopoietic stem cell ageing and rejuvenation by inhibiting p38 kinase activity. Nat. Commun. 7, 13674 (2016).",{"doi":2817},"10.1038\u002Fncomms13674",{"id":24,"text":2819,"url":24,"identifiers":2820},"Joshi, S., Kaur, S., Kroczynska, B. & Platanias, L. C. Mechanisms of mRNA translation of interferon stimulated genes. Cytokine 52, 123–127 (2010).",{"doi":2821},"10.1016\u002Fj.cyto.2010.03.019",{"id":24,"text":2823,"url":24,"identifiers":2824},"Maik-Rachline, G., Lifshits, L. & Seger, R. Nuclear P38: roles in physiological and pathological processes and regulation of nuclear translocation. Int. J. Mol. Sci. 21, 6102 (2020).",{"doi":2825},"10.3390\u002Fijms21176102",{"id":24,"text":2827,"url":24,"identifiers":2828},"Thornton, T. M. et al. Inactivation of nuclear GSK3β by Ser389 phosphorylation promotes lymphocyte fitness during DNA double-strand break response. Nat. Commun. 7, 10553 (2016).",{"doi":2829},"10.1038\u002Fncomms10553",{"id":24,"text":2831,"url":24,"identifiers":2832},"Reinhardt, H. C., Aslanian, A. S., Lees, J. A. & Yaffe, M. B. p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK\u002FMK2 pathway for survival after DNA damage. Cancer Cell 11, 175–189 (2007).",{"doi":2833},"10.1016\u002Fj.ccr.2006.11.024",{"id":24,"text":2835,"url":24,"identifiers":2836},"Zhang, Y. et al. PP2AC level determines differential programming of p38–TSC–mTOR signaling and therapeutic response to p38-targeted therapy in colorectal cancer. EBioMedicine 2, 1944–1956 (2015).",{"doi":2837},"10.1016\u002Fj.ebiom.2015.11.031",{"id":24,"text":2839,"url":24,"identifiers":2840},"Kim, D. H. et al. A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 297, 623–626 (2002).",{"doi":2841},"10.1126\u002Fscience.1073759",{"id":24,"text":2843,"url":24,"identifiers":2844},"Gupta, J. & Nebreda, A. R. Roles of p38α mitogen-activated protein kinase in mouse models of inflammatory diseases and cancer. FEBS J. 282, 1841–1857 (2015).",{"doi":2845},"10.1111\u002Ffebs.13250",{"id":24,"text":2847,"url":24,"identifiers":2848},"Rincon, M. & Davis, R. J. Regulation of the immune response by stress-activated protein kinases. Immunol. Rev. 228, 212–224 (2009).",{"doi":2849},"10.1111\u002Fj.1600-065X.2008.00744.x",{"id":24,"text":2851,"url":24,"identifiers":2852},"Gurusamy, D. et al. Multi-phenotype CRISPR–Cas9 screen identifies p38 kinase as a target for adoptive immunotherapies. Cancer Cell 37, 818–833.e9 (2020). This paper identifies the p38 kinase pathway as a central regulator of several phenotypes associated with the antitumour efficacy of T cells.",{"doi":2853},"10.1016\u002Fj.ccell.2020.05.004",{"id":24,"text":2855,"url":24,"identifiers":2856},"Navarrete, M. et al. Astrocytic p38α MAPK drives NMDA receptor-dependent long-term depression and modulates long-term memory. Nat. Commun. 10, 2968 (2019).",{"doi":2857},"10.1038\u002Fs41467-019-10830-9",{"id":24,"text":2859,"url":24,"identifiers":2860},"Bolshakov, V. Y. et al. Dual MAP kinase pathways mediate opposing forms of long-term plasticity at CA3–CA1 synapses. Nat. Neurosci. 3, 1107–1112 (2000).",{"doi":2861},"10.1038\u002F80624",{"id":24,"text":2863,"url":24,"identifiers":2864},"Zhu, J. J., Qin, Y., Zhao, M., Van Aelst, L. & Malinow, R. Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell 110, 443–455 (2002).",{"doi":2865},"10.1016\u002FS0092-8674(02)00897-8",{"id":24,"text":2867,"url":24,"identifiers":2868},"Chung, S. H. et al. The p38α mitogen-activated protein kinase is a key regulator of myelination and remyelination in the CNS. Cell Death Dis. 6, e1748 (2015).",{"doi":2869},"10.1038\u002Fcddis.2015.119",{"id":24,"text":2871,"url":24,"identifiers":2872},"Haines, J. D., Fragoso, G., Hossain, S., Mushynski, W. E. & Almazan, G. p38 mitogen-activated protein kinase regulates myelination. J. Mol. Neurosci. 35, 23–33 (2008).",{"doi":2873},"10.1007\u002Fs12031-007-9011-0",{"id":24,"text":2875,"url":24,"identifiers":2876},"Liu, X. et al. BMP7 retards peripheral myelination by activating p38 MAPK in Schwann cells. Sci. Rep. 6, 31049 (2016).",{"doi":2877},"10.1038\u002Fsrep31049",{"id":24,"text":2879,"url":24,"identifiers":2880},"Lin, X., Wang, M., Zhang, J. & Xu, R. p38 MAPK: a potential target of chronic pain. Curr. Med. Chem. 21, 4405–4418 (2014).",{"doi":2881},"10.2174\u002F0929867321666140915143040",{"id":24,"text":2883,"url":24,"identifiers":2884},"Scheltens, P. et al. An exploratory clinical study of p38α kinase inhibition in Alzheimer’s disease. Ann. Clin. Transl. Neurol. 5, 464–473 (2018).",{"doi":2885},"10.1002\u002Facn3.549",{"id":24,"text":2887,"url":24,"identifiers":2888},"Hensley, K. et al. p38 kinase is activated in the Alzheimer’s disease brain. J. Neurochem. 72, 2053–2058 (1999).",{"doi":2889},"10.1046\u002Fj.1471-4159.1999.0722053.x",{"id":24,"text":2891,"url":24,"identifiers":2892},"Zhu, X. et al. Activation of MKK6, an upstream activator of p38, in Alzheimer’s disease. J. Neurochem. 79, 311–318 (2001).",{"doi":2893},"10.1046\u002Fj.1471-4159.2001.00597.x",{"id":24,"text":2895,"url":24,"identifiers":2896},"Sun, A., Liu, M., Nguyen, X. V. & Bing, G. P38 MAP kinase is activated at early stages in Alzheimer’s disease brain. Exp. Neurol. 183, 394–405 (2003).",{"doi":2897},"10.1016\u002FS0014-4886(03)00180-8",{"id":24,"text":2899,"url":24,"identifiers":2900},"Du, Y. et al. MKP-1 reduces Aβ generation and alleviates cognitive impairments in Alzheimer’s disease models. Signal. Transduct. Target. Ther. 4, 58 (2019).",{"doi":2901},"10.1038\u002Fs41392-019-0091-4",{"id":24,"text":2903,"url":24,"identifiers":2904},"Kheiri, G., Dolatshahi, M., Rahmani, F. & Rezaei, N. Role of p38\u002FMAPKs in Alzheimer’s disease: implications for amyloid β toxicity targeted therapy. Rev. Neurosci. 30, 9–30 (2018).",{"doi":2905},"10.1515\u002Frevneuro-2018-0008",{"id":24,"text":2907,"url":24,"identifiers":2908},"Lee, J. K. & Kim, N. J. Recent advances in the inhibition of p38 MAPK as a potential strategy for the treatment of Alzheimer’s disease. Molecules 22, 1287 (2017).",{"doi":2909},"10.3390\u002Fmolecules22081287",{"id":24,"text":2911,"url":24,"identifiers":2912},"Colie, S. et al. Neuronal p38α mediates synaptic and cognitive dysfunction in an Alzheimer’s mouse model by controlling β-amyloid production. Sci. Rep. 7, 45306 (2017).",{"doi":2913},"10.1038\u002Fsrep45306",{"id":24,"text":2915,"url":24,"identifiers":2916},"Thomas, T. et al. MAPKAP kinase 2-deficiency prevents neurons from cell death by reducing neuroinflammation—relevance in a mouse model of Parkinson’s disease. J. Neurochem. 105, 2039–2052 (2008).",{"doi":2917},"10.1111\u002Fj.1471-4159.2008.05310.x",{"id":24,"text":2919,"url":24,"identifiers":2920},"Dewil, M., dela Cruz, V. F., Van Den Bosch, L. & Robberecht, W. Inhibition of p38 mitogen activated protein kinase activation and mutant SOD1(G93A)-induced motor neuron death. Neurobiol. Dis. 26, 332–341 (2007).",{"doi":2921},"10.1016\u002Fj.nbd.2006.12.023",{"id":24,"text":2923,"url":24,"identifiers":2924},"Bendotti, C. et al. Activated p38MAPK is a novel component of the intracellular inclusions found in human amyotrophic lateral sclerosis and mutant SOD1 transgenic mice. J. Neuropathol. Exp. Neurol. 63, 113–119 (2004).",{"doi":2925},"10.1093\u002Fjnen\u002F63.2.113",{"id":24,"text":2927,"url":24,"identifiers":2928},"Gibbs, K. L. et al. Inhibiting p38 MAPKα rescues axonal retrograde transport defects in a mouse model of ALS. Cell Death Dis. 9, 596 (2018).",{"doi":2929},"10.1038\u002Fs41419-018-0624-8",{"id":24,"text":2931,"url":24,"identifiers":2932},"Bhinge, A., Namboori, S. C., Zhang, X., VanDongen, A. M. J. & Stanton, L. W. Genetic correction of SOD1 mutant iPSCs reveals ERK and JNK activated AP1 as a driver of neurodegeneration in amyotrophic lateral sclerosis. Stem Cell Rep. 8, 856–869 (2017).",{"doi":2933},"10.1016\u002Fj.stemcr.2017.02.019",{"id":24,"text":2935,"url":24,"identifiers":2936},"Robson, M. J. et al. p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse. Proc. Natl Acad. Sci. USA 115, E10245–E10254 (2018).",{"doi":2937},"10.1073\u002Fpnas.1809137115",{"id":24,"text":2939,"url":24,"identifiers":2940},"Arabacilar, P. & Marber, M. The case for inhibiting p38 mitogen-activated protein kinase in heart failure. Front. Pharmacol. 6, 102 (2015).",{"doi":2941},"10.3389\u002Ffphar.2015.00102",{"id":24,"text":2943,"url":24,"identifiers":2944},"Martin, E. D., Bassi, R. & Marber, M. S. p38 MAPK in cardioprotection—are we there yet? Br. J. Pharmacol. 172, 2101–2113 (2015).",{"doi":2945},"10.1111\u002Fbph.12901",{"id":24,"text":2947,"url":24,"identifiers":2948},"Newby, L. K. et al. Losmapimod, a novel p38 mitogen-activated protein kinase inhibitor, in non-ST-segment elevation myocardial infarction: a randomised phase 2 trial. Lancet 384, 1187–1195 (2014).",{"doi":2949},"10.1016\u002FS0140-6736(14)60417-7",{"id":24,"text":2951,"url":24,"identifiers":2952},"O’Donoghue, M. L. et al. Effect of losmapimod on cardiovascular outcomes in patients hospitalized with acute myocardial infarction: a randomized clinical trial. JAMA 315, 1591–1599 (2016).",{"doi":2953},"10.1001\u002Fjama.2016.3609",{"id":24,"text":2955,"url":24,"identifiers":2956},"Meng, Q. et al. MMI-0100 inhibits cardiac fibrosis in a mouse model overexpressing cardiac myosin binding protein C. J. Am. Heart Assoc. 6, e006590 (2017).",{"doi":2957},"10.1161\u002FJAHA.117.006590",{"id":24,"text":2959,"url":24,"identifiers":2960},"Wang, Q. et al. Disruption of TAB1\u002Fp38α interaction using a cell-permeable peptide limits myocardial ischemia\u002Freperfusion injury. Mol. Ther. 21, 1668–1677 (2013).",{"doi":2961},"10.1038\u002Fmt.2013.90",{"id":24,"text":2963,"url":24,"identifiers":2964},"Manieri, E. & Sabio, G. Stress kinases in the modulation of metabolism and energy balance. J. Mol. Endocrinol. 55, R11–R22 (2015).",{"doi":2965},"10.1530\u002FJME-15-0146",{"id":24,"text":2967,"url":24,"identifiers":2968},"Zhang, S. et al. Metabolic benefits of inhibition of p38α in white adipose tissue in obesity. PLoS Biol. 16, e2004225 (2018).",{"doi":2969},"10.1371\u002Fjournal.pbio.2004225",{"id":24,"text":2971,"url":24,"identifiers":2972},"Berry, D. C. et al. Cellular aging contributes to failure of cold-induced beige adipocyte formation in old mice and humans. Cell Metab. 25, 166–181 (2017).",{"doi":2973},"10.1016\u002Fj.cmet.2016.10.023",{"id":24,"text":2975,"url":24,"identifiers":2976},"Zhang, X. et al. Macrophage p38α promotes nutritional steatohepatitis through M1 polarization. J. Hepatol. 71, 163–174 (2019).",{"doi":2977},"10.1016\u002Fj.jhep.2019.03.014",{"id":24,"text":2979,"url":24,"identifiers":2980},"Puigserver, P. et al. Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARγ coactivator-1. Mol. Cell 8, 971–982 (2001).",{"doi":2981},"10.1016\u002FS1097-2765(01)00390-2",{"id":24,"text":2983,"url":24,"identifiers":2984},"Brown, J. L. et al. Protein imbalance in the development of skeletal muscle wasting in tumour-bearing mice. J. Cachexia Sarcopenia Muscle 9, 987–1002 (2018).",{"doi":2985},"10.1002\u002Fjcsm.12354",{"id":24,"text":2987,"url":24,"identifiers":2988},"Bulavin, D. V. & Fornace, A. J. Jr. p38 MAP kinase’s emerging role as a tumor suppressor. Adv. Cancer Res. 92, 95–118 (2004).",{"doi":2989},"10.1016\u002FS0065-230X(04)92005-2",{"id":24,"text":2991,"url":24,"identifiers":2992},"Loesch, M. & Chen, G. The p38 MAPK stress pathway as a tumor suppressor or more? Front. Biosci. 13, 3581–3593 (2008).",{"doi":2993},"10.2741\u002F2951",{"id":24,"text":2995,"url":24,"identifiers":2996},"Hui, L. et al. p38α suppresses normal and cancer cell proliferation by antagonizing the JNK–c-Jun pathway. Nat. Genet. 39, 741–749 (2007).",{"doi":2997},"10.1038\u002Fng2033",{"id":24,"text":2999,"url":24,"identifiers":3000},"Ventura, J. J. et al. p38α MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat. Genet. 39, 750–758 (2007).",{"doi":3001},"10.1038\u002Fng2037",{"id":24,"text":3003,"url":24,"identifiers":3004},"Gupta, J. et al. Dual function of p38α MAPK in colon cancer: suppression of colitis-associated tumor initiation but requirement for cancer cell survival. Cancer Cell 25, 484–500 (2014). This study describes pro-tumorigenic and anti-tumorigenic functions of p38α in the same mouse model of cancer depending on the tumorigenesis stage.",{"doi":3005},"10.1016\u002Fj.ccr.2014.02.019",{"id":24,"text":3007,"url":24,"identifiers":3008},"Igea, A. & Nebreda, A. R. The stress kinase p38α as a target for cancer therapy. Cancer Res. 75, 3997–4002 (2015). This paper presents an overview of the cell autonomous roles of p38α in cancer cells.",{"doi":3009},"10.1158\u002F0008-5472.CAN-15-0173",{"id":24,"text":3011,"url":24,"identifiers":3012},"Vitos-Faleato, J. et al. Requirement for epithelial p38α in KRAS-driven lung tumor progression. Proc. Natl Acad. Sci. USA 117, 2588–2596 (2020).",{"doi":3013},"10.1073\u002Fpnas.1921404117",{"id":24,"text":3015,"url":24,"identifiers":3016},"Saad, M. I. et al. ADAM17 selectively activates the IL-6 trans-signaling\u002FERK MAPK axis in KRAS-addicted lung cancer. EMBO Mol. Med. 11, e9976 (2019).",{"doi":3017},"10.15252\u002Femmm.201809976",{"id":24,"text":3019,"url":24,"identifiers":3020},"Wu, X. et al. Ubiquitin-conjugating enzyme Ubc13 controls breast cancer metastasis through a TAK1–p38 MAP kinase cascade. Proc. Natl Acad. Sci. USA 111, 13870–13875 (2014).",{"doi":3021},"10.1073\u002Fpnas.1414358111",{"id":24,"text":3023,"url":24,"identifiers":3024},"Tichet, M. et al. Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis. Nat. Commun. 6, 6993 (2015).",{"doi":3025},"10.1038\u002Fncomms7993",{"id":24,"text":3027,"url":24,"identifiers":3028},"Anwar, T. et al. p38-mediated phosphorylation at T367 induces EZH2 cytoplasmic localization to promote breast cancer metastasis. Nat. Commun. 9, 2801 (2018).",{"doi":3029},"10.1038\u002Fs41467-018-05078-8",{"id":24,"text":3031,"url":24,"identifiers":3032},"Ryu, K. J. et al. p38 stabilizes Snail by suppressing DYRK2-mediated phosphorylation that is required for GSK3β–βTrCP-induced Snail degradation. Cancer Res. 79, 4135–4148 (2019).",{"doi":3033},"10.1158\u002F0008-5472.CAN-19-0049",{"id":24,"text":3035,"url":24,"identifiers":3036},"Naffa, R. et al. p38 MAPK promotes migration and metastatic activity of BRAF mutant melanoma cells by inducing degradation of PMCA4b. Cells 9, 1209 (2020).",{"doi":3037},"10.3390\u002Fcells9051209",{"id":24,"text":3039,"url":24,"identifiers":3040},"Harper, K. L. et al. Mechanism of early dissemination and metastasis in Her2+ mammary cancer. Nature 540, 588–592 (2016).",{"doi":3041},"10.1038\u002Fnature20609",{"id":24,"text":3043,"url":24,"identifiers":3044},"Urosevic, J. et al. Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signalling and PTHLH. Nat. Cell Biol. 16, 685–694 (2014).",{"doi":3045},"10.1038\u002Fncb2977",{"id":24,"text":3047,"url":24,"identifiers":3048},"Gawrzak, S. et al. MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer. Nat. Cell Biol. 20, 211–221 (2018).",{"doi":3049},"10.1038\u002Fs41556-017-0021-z",{"id":24,"text":3051,"url":24,"identifiers":3052},"Brichkina, A. et al. p38MAPK builds a hyaluronan cancer niche to drive lung tumorigenesis. Genes Dev. 30, 2623–2636 (2016).",{"doi":3053},"10.1101\u002Fgad.290346.116",{"id":24,"text":3055,"url":24,"identifiers":3056},"Curtis, M. et al. Fibroblasts mobilize tumor cell glycogen to promote proliferation and metastasis. Cell Metab. 29, 141–155.e9 (2019). This interesting study on the interplay between fibroblasts and cancer cells shows how p38α signalling in fibroblasts can modulate the metabolism of cancer cells.",{"doi":3057},"10.1016\u002Fj.cmet.2018.08.007",{"id":24,"text":3059,"url":24,"identifiers":3060},"Suarez-Lopez, L. et al. MK2 contributes to tumor progression by promoting M2 macrophage polarization and tumor angiogenesis. Proc. Natl Acad. Sci. USA 115, E4236–E4244 (2018).",{"doi":3061},"10.1073\u002Fpnas.1722020115",{"id":24,"text":3063,"url":24,"identifiers":3064},"Alam, M. S. et al. Selective inhibition of the p38 alternative activation pathway in infiltrating T cells inhibits pancreatic cancer progression. Nat. Med. 21, 1337–1343 (2015).",{"doi":3065},"10.1038\u002Fnm.3957",{"id":24,"text":3067,"url":24,"identifiers":3068},"Zonneville, J. et al. Blockade of p38 kinase impedes the mobilization of protumorigenic myeloid populations to impact breast cancer metastasis. Int. J. Cancer 147, 2279–2292 (2020).",{"doi":3069},"10.1002\u002Fijc.33050",{"id":24,"text":3071,"url":24,"identifiers":3072},"Santoro, V. et al. Role of reactive oxygen species in the abrogation of oxaliplatin activity by cetuximab in colorectal cancer. J. Natl Cancer Inst. 108, djv394 (2016).",{"doi":3073},"10.1093\u002Fjnci\u002Fdjv394",{"id":24,"text":3075,"url":24,"identifiers":3076},"Garcia-Cano, J. et al. p38MAPK and chemotherapy: we always need to hear both sides of the story. Front. Cell Dev. Biol. 4, 69 (2016).",{"doi":3077},"10.3389\u002Ffcell.2016.00069",{"id":24,"text":3079,"url":24,"identifiers":3080},"Lin, A. et al. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci. Transl Med. 11, eaaw841 (2019).",{"doi":3081},"10.1126\u002Fscitranslmed.aaw8412",{"id":24,"text":3083,"url":24,"identifiers":3084},"Pereira, L., Igea, A., Canovas, B., Dolado, I. & Nebreda, A. R. Inhibition of p38 MAPK sensitizes tumour cells to cisplatin-induced apoptosis mediated by reactive oxygen species and JNK. EMBO Mol. Med. 5, 1759–1774 (2013).",{"doi":3085},"10.1002\u002Femmm.201302732",{"id":24,"text":3087,"url":24,"identifiers":3088},"Rudalska, R. et al. In vivo RNAi screening identifies a mechanism of sorafenib resistance in liver cancer. Nat. Med. 20, 1138–1146 (2014).",{"doi":3089},"10.1038\u002Fnm.3679",{"id":24,"text":3091,"url":24,"identifiers":3092},"Dietlein, F. et al. A synergistic interaction between Chk1- and MK2 inhibitors in KRAS-mutant cancer. Cell 162, 146–159 (2015).",{"doi":3093},"10.1016\u002Fj.cell.2015.05.053",{"id":24,"text":3095,"url":24,"identifiers":3096},"Lalaoui, N. et al. Targeting p38 or MK2 enhances the anti-leukemic activity of smac-mimetics. Cancer Cell 29, 145–158 (2016). This article shows an interesting cooperation between the inhibitors of p38 or MK2 and Smac-mimetic drugs in leukaemia cells, and paves the way for the discovery of an important link between p38\u002FMK2 and RIPK in the inflammatory response.",{"doi":3097},"10.1016\u002Fj.ccell.2016.01.006",{"id":24,"text":3099,"url":24,"identifiers":3100},"Murali, B. et al. Inhibition of the stromal p38MAPK\u002FMK2 pathway limits breast cancer metastases and chemotherapy-induced bone loss. Cancer Res. 78, 5618–5630 (2018).",{"doi":3101},"10.1158\u002F0008-5472.CAN-18-0234",{"id":24,"text":3103,"url":24,"identifiers":3104},"MacNee, W., Allan, R. J., Jones, I., De Salvo, M. C. & Tan, L. F. Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease: a randomised clinical trial. Thorax 68, 738–745 (2013).",{"doi":3105},"10.1136\u002Fthoraxjnl-2012-202744",{"id":24,"text":3107,"url":24,"identifiers":3108},"Godl, K. et al. An efficient proteomics method to identify the cellular targets of protein kinase inhibitors. Proc. Natl Acad. Sci. USA 100, 15434–15439 (2003).",{"doi":3109},"10.1073\u002Fpnas.2535024100",{"id":24,"text":3111,"url":24,"identifiers":3112},"Jones, D. S., Jenney, A. P., Joughin, B. A., Sorger, P. K. & Lauffenburger, D. A. Inflammatory but not mitogenic contexts prime synovial fibroblasts for compensatory signaling responses to p38 inhibition. Sci. Signal. 11, eaal1601 (2018).",{"doi":3113},"10.1126\u002Fscisignal.aal1601",{"id":24,"text":3115,"url":24,"identifiers":3116},"Wang, C. et al. Selective inhibition of the p38α MAPK–MK2 axis inhibits inflammatory cues including inflammasome priming signals. J. Exp. Med. 215, 1315–1325 (2018).",{"doi":3117},"10.1084\u002Fjem.20172063",{"id":24,"text":3119,"url":24,"identifiers":3120},"Patnaik, A. et al. A first-in-human phase I study of the oral p38 MAPK inhibitor, ralimetinib (LY2228820 dimesylate), in patients with advanced cancer. Clin. Cancer Res. 22, 1095–1102 (2016).",{"doi":3121},"10.1158\u002F1078-0432.CCR-15-1718",{"id":24,"text":3123,"url":24,"identifiers":3124},"Vergote, I. et al. A randomized, double-blind, placebo-controlled phase 1b\u002F2 study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine and carboplatin versus gemcitabine and carboplatin for women with recurrent platinum-sensitive ovarian cancer. Gynecol. Oncol. 156, 23–31 (2020).",{"doi":3125},"10.1016\u002Fj.ygyno.2019.11.006",{"id":24,"text":3127,"url":24,"identifiers":3128},"Donoghue, C. et al. Optimal linker length for small molecule PROTACs that selectively target p38α and p38β for degradation. Eur. J. Med. Chem. 201, 112451 (2020).",{"doi":3129},"10.1016\u002Fj.ejmech.2020.112451",{"id":24,"text":3131,"url":24,"identifiers":3132},"Casadome-Perales, A. et al. Inhibition of p38 MAPK in the brain through nasal administration of p38 inhibitor loaded in chitosan nanocapsules. Nanomedicine 14, 2409–2422 (2019).",{"doi":3133},"10.2217\u002Fnnm-2018-0496",{"id":24,"text":3135,"url":24,"identifiers":3136},"Maik-Rachline, G., Zehorai, E., Hanoch, T., Blenis, J. & Seger, R. The nuclear translocation of the kinases p38 and JNK promotes inflammation-induced cancer. Sci. Signal. 11, eaao3428 (2018).",{"doi":3137},"10.1126\u002Fscisignal.aao3428",{"id":24,"text":3139,"url":24,"identifiers":3140},"Martinez-Limon, A., Joaquin, M., Caballero, M., Posas, F. & de Nadal, E. The p38 pathway: from biology to cancer therapy. Int. J. Mol. Sci. 21, 1913 (2020).",{"doi":3141},"10.3390\u002Fijms21061913",{"id":24,"text":3143,"url":24,"identifiers":3144},"Gee, M. S. et al. A selective p38α\u002Fβ MAPK inhibitor alleviates neuropathology and cognitive impairment, and modulates microglia function in 5XFAD mouse. Alzheimers Res. Ther. 12, 45 (2020).",{"doi":3145},"10.1186\u002Fs13195-020-00617-2",{"id":24,"text":3147,"url":24,"identifiers":3148},"Roy, S. M. et al. Targeting human central nervous system protein kinases: an isoform selective p38αMAPK inhibitor that attenuates disease progression in Alzheimer’s disease mouse models. ACS Chem. Neurosci. 6, 666–680 (2015).",{"doi":3149},"10.1021\u002Facschemneuro.5b00002",{"id":24,"text":3151,"url":24,"identifiers":3152},"Evans, B. C. et al. MK2 inhibitory peptide delivered in nanopolyplexes prevents vascular graft intimal hyperplasia. Sci. Transl Med. 7, 291ra295 (2015).",{"doi":3153},"10.1126\u002Fscitranslmed.aaa4549",{"id":24,"text":3155,"url":24,"identifiers":3156},"Sies, H. & Jones, D. P. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat. Rev. Mol. Cell Biol. 21, 363–383 (2020).",{"doi":3157},"10.1038\u002Fs41580-020-0230-3",{"id":24,"text":3159,"url":24,"identifiers":3160},"Asih, P. R. et al. Functions of p38 MAP kinases in the central nervous system. Front. Mol. Neurosci. 13, 570586 (2020).",{"doi":3161},"10.3389\u002Ffnmol.2020.570586",{"id":24,"text":3163,"url":24,"identifiers":3164},"Kuzmanic, A. et al. Changes in the free-energy landscape of p38α MAP kinase through its canonical activation and binding events as studied by enhanced molecular dynamics simulations. eLife 6, e22175 (2017).",{"doi":3165},"10.7554\u002FeLife.22175",{"id":24,"text":3167,"url":24,"identifiers":3168},"Tokunaga, Y., Takeuchi, K., Takahashi, H. & Shimada, I. Allosteric enhancement of MAP kinase p38α’s activity and substrate selectivity by docking interactions. Nat. Struct. Mol. Biol. 21, 704–711 (2014).",{"doi":3169},"10.1038\u002Fnsmb.2861",{"id":24,"text":3171,"url":24,"identifiers":3172},"Kumar, G. S. et al. Dynamic activation and regulation of the mitogen-activated protein kinase p38. Proc. Natl Acad. Sci. USA 115, 4655–4660 (2018). Together with Kuzmanic et al. (2017) and Tokunaga et al. (2014), this paper provides detailed insights into the mechanism of p38α kinase activation using NMR and molecular modelling.",{"doi":3173},"10.1073\u002Fpnas.1721441115",{"id":24,"text":3175,"url":24,"identifiers":3176},"Haller, V., Nahidino, P., Forster, M. & Laufer, S. A. An updated patent review of p38 MAP kinase inhibitors (2014–2019). Expert Opin. Ther. Pat. 30, 453–466 (2020).",{"doi":3177},"10.1080\u002F13543776.2020.1749263",{"id":24,"text":3179,"url":24,"identifiers":3180},"Yang, L. et al. p38α mitogen-activated protein kinase is a druggable target in pancreatic adenocarcinoma. Front. Oncol. 9, 1294 (2019).",{"doi":3181},"10.3389\u002Ffonc.2019.01294",{"id":24,"text":3183,"url":24,"identifiers":3184},"Shah, N. G. et al. Novel noncatalytic substrate-selective p38α-specific MAPK inhibitors with endothelial-stabilizing and anti-inflammatory activity. J. Immunol. 198, 3296–3306 (2017).",{"doi":3185},"10.4049\u002Fjimmunol.1602059",{"id":24,"text":3187,"url":24,"identifiers":3188},"Nichols, C. et al. Mining the PDB for tractable cases where X-ray crystallography combined with fragment screens can be used to systematically design protein–protein inhibitors: two test cases illustrated by IL1β–IL1R and p38α–TAB1 complexes. J. Med. Chem. 63, 7559–7568 (2020).",{"doi":3189},"10.1021\u002Facs.jmedchem.0c00403",{"id":24,"text":3191,"url":24,"identifiers":3192},"Lemmens, B. et al. DNA replication determines timing of mitosis by restricting CDK1 and PLK1 activation. Mol. Cell 71, 117–128.e3 (2018).",{"doi":3193},"10.1016\u002Fj.molcel.2018.05.026",{"id":24,"text":3195,"url":24,"identifiers":3196},"Thornton, T. M. et al. Phosphorylation by p38 MAPK as an alternative pathway for GSK3β inactivation. Science 320, 667–670 (2008).",{"doi":3197},"10.1126\u002Fscience.1156037",{"id":24,"text":3199,"url":24,"identifiers":3200},"Cully, M. et al. A role for p38 stress-activated protein kinase in regulation of cell growth via TORC1. Mol. Cell Biol. 30, 481–495 (2010).",{"doi":3201},"10.1128\u002FMCB.00688-09",{"id":24,"text":3203,"url":24,"identifiers":3204},"Li, L. et al. TLR8-mediated metabolic control of human Treg function: a mechanistic target for cancer immunotherapy. Cell Metab. 29, 103–123.e5 (2019).",{"doi":3205},"10.1016\u002Fj.cmet.2018.09.020",{"id":24,"text":3207,"url":24,"identifiers":3208},"Hernandez, G. et al. A novel cardioprotective p38-MAPK\u002FmTOR pathway. Exp. Cell Res. 317, 2938–2949 (2011).",{"doi":3209},"10.1016\u002Fj.yexcr.2011.09.011",{"id":3211,"createTime":3212,"updateTime":3212,"relativeEntities":3213,"slug":3214,"properties":3215,"entityType":131,"verifyStatus":132,"verifyTime":3226,"verifyNote":133,"languages":3227,"translateLanguages":24,"viewCount":25,"primaryUrl":3228,"fullTextUrl":24,"authors":3229,"publicationType":174,"publisherRelationship":3268,"citationCount":3321,"citationInfo":3322,"publishDate":3335,"publishYear":3323,"citationAnalyzeStatus":23,"lastCitationAnalyze":24,"indexDatabases":3336,"openAccess":24,"references":3337,"isForceReanalyzing":409},"5b8902f2-3cbc-47cc-a920-8348c5312869","2025-02-09T21:35:31.520+00:00",[],"TGF%CE%B2-SMAD-signal-transduction-molecular-specificity-and-functional-flexibility",{"openalex":3216,"mag":3218,"title":3220,"pm":3222,"doi":3224},{"VOID":3217},"W1528120845",{"VOID":3219},"1528120845",{"EN":3221},"TGFβ–SMAD signal transduction: molecular specificity and functional flexibility",{"VOID":3223},"18000526",{"VOID":3225},"10.1038\u002Fnrm2297","2025-02-09T21:35:31.519+00:00",[135],"https:\u002F\u002Fwww.nature.com\u002Farticles\u002Fnrm2297",[3230,3249],{"id":3231,"sortIndex":25,"researcher":24,"roles":3232,"affiliations":3233,"properties":3242,"displayName":3246,"givenName":24,"familyName":24},"b40a37bb-ef9a-4ac7-963c-ade915f40972",[],[3234],{"id":3235,"sortIndex":25,"affiliation":3236,"properties":24},"90b640fb-aabd-45c6-8d2c-66694df07a66",{"id":3235,"createTime":24,"updateTime":24,"relativeEntities":3237,"slug":24,"properties":3238,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":3241,"statistic":24},[],{"title":3239},{"EN":3240},"Developmental Signalling Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.",[],{"orcid":3243,"title":3245,"openalex":3247},{"VOID":3244},"https:\u002F\u002Forcid.org\u002F0000-0002-9082-7022",{"EN":3246},"Bernhard Schmierer",{"VOID":3248},"A5014947747",{"id":3250,"sortIndex":99,"researcher":24,"roles":3251,"affiliations":3252,"properties":3261,"displayName":3265,"givenName":24,"familyName":24},"d3131937-4a07-4151-95ff-2ea24f4e8c7e",[],[3253],{"id":3254,"sortIndex":25,"affiliation":3255,"properties":24},"cf221ea1-6ba1-41f7-b7e4-480a5a11abdf",{"id":3254,"createTime":24,"updateTime":24,"relativeEntities":3256,"slug":24,"properties":3257,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":3260,"statistic":24},[],{"title":3258},{"EN":3259},"Developmental Signalling Laboratory, Cancer Research UK London Research Institute, London, UK",[],{"orcid":3262,"title":3264,"openalex":3266},{"VOID":3263},"https:\u002F\u002Forcid.org\u002F0000-0002-8632-0480",{"EN":3265},"Caroline S. Hill",{"VOID":3267},"A5035380866",{"url":24,"publisher":3269,"properties":3316},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":3270,"slug":10,"properties":3271,"entityType":22,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":25,"subjectFields":3276,"manageAffiliations":3285,"indexDatabases":3296,"url":90,"thumbnailPath":24,"statistic":3311,"gsStatistic":24,"type":24,"analyzePriority":24},[],{"country":3272,"eissn":3273,"issn":3274,"title":3275},{"VOID":13},{"VOID":15},{"VOID":17},{"EN":19},[3277,3281],{"id":28,"createTime":24,"updateTime":24,"relativeEntities":3278,"label":3279,"description":3280,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":31},{},{"id":34,"createTime":24,"updateTime":24,"relativeEntities":3282,"label":3283,"description":3284,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":37},{},[3286,3291],{"id":41,"createTime":24,"updateTime":24,"relativeEntities":3287,"slug":24,"properties":3288,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":3290,"statistic":24},[],{"title":3289},{"EN":45},[],{"id":48,"createTime":24,"updateTime":24,"relativeEntities":3292,"slug":24,"properties":3293,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":3295,"statistic":24},[],{"title":3294},{"EN":52},[],[3297,3304],{"id":56,"indexDatabase":3298,"url":69,"indexYears":24,"academicFieldIds":3303,"indexDatabaseRanking":24},{"id":58,"createTime":24,"updateTime":24,"relativeEntities":3299,"label":3300,"description":3301,"key":65,"publicationTags":3302,"standard":24},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":3305,"url":84,"indexYears":85,"academicFieldIds":3310,"indexDatabaseRanking":89},{"id":75,"createTime":24,"updateTime":24,"relativeEntities":3306,"label":3307,"description":3308,"key":81,"publicationTags":3309,"standard":24},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88],{"impactFactor":25,"impactFactorByYear":3312,"i10Index":97,"i10IndexLast5Year":25,"totalPublication":97,"totalPublicationByYear":3313,"totalCitation":100,"totalCitationByYear":3314,"totalCitationPerPublication":106,"totalCitationPerPublicationByYear":3315,"hindexLast5Year":97,"hindex":97},{"2016":93,"2017":94,"2019":95,"2020":96},{"2007":99,"2009":99,"2015":99,"2018":99},{"2007":102,"2009":103,"2015":104,"2018":105},{"2007":102,"2009":103,"2015":104,"2018":105},{"issue":3317,"pages":3318,"volume":3320},{"VOID":1787},{"VOID":3319},"970-982",{"VOID":1102},1203,{"total":3321,"publishYear":3323,"statisticByYear":3324},2007,{"2012":3325,"2013":3326,"2014":3327,"2015":3328,"2016":3329,"2017":3330,"2018":3331,"2019":3332,"2020":1116,"2021":3333,"2022":3330,"2023":3334,"2024":3329,"2025":1016},94,77,58,78,53,65,74,56,76,67,"2007-12-01",[67,89],[3338,3342,3346,3350,3354,3358,3362,3366,3370,3374,3378,3382,3386,3390,3394,3398,3402,3406,3410,3414,3418,3422,3426,3430,3434,3438,3442,3446,3450,3454,3458,3462,3466,3470,3474,3478,3482,3486,3490,3494,3498,3502,3506,3510,3514,3518,3522,3526,3530,3534,3538,3542,3546,3550,3554,3558,3562,3566,3570,3574,3578,3582,3586,3590,3594,3598,3602,3606,3610,3614,3618,3622,3626,3630,3634,3638,3642,3646,3650,3654,3658,3662,3666,3670,3674,3678,3682,3686,3690,3694,3698,3702,3706,3710,3714,3718,3722,3726,3730,3734,3738,3742,3746,3750,3754,3758,3762,3766,3770,3774,3778,3782,3786,3790,3794,3798,3802,3806,3810,3814,3818,3822,3826,3830,3834,3838,3842,3846,3850,3854,3858,3862,3866,3870,3874,3878,3882,3886,3890,3894,3898],{"id":24,"text":3339,"url":24,"identifiers":3340},"Blobe, G. C., Schiemann, W. P. & Lodish, H. F. Role of transforming growth factor β in human disease. N. Engl. J. Med. 342, 1350–1358 (2000).",{"doi":3341},"10.1056\u002FNEJM200005043421807",{"id":24,"text":3343,"url":24,"identifiers":3344},"Massagué, J., Blain, S. W. & Lo, R. S. TGFβ signaling in growth control, cancer, and heritable disorders. Cell 103, 295–309 (2000).",{"doi":3345},"10.1016\u002FS0092-8674(00)00121-5",{"id":24,"text":3347,"url":24,"identifiers":3348},"Gray, A. M. & Mason, A. J. Requirement for activin A and transforming growth factor-β1 pro-regions in homodimer assembly. Science 247, 1328–1330 (1990).",{"doi":3349},"10.1126\u002Fscience.2315700",{"id":24,"text":3351,"url":24,"identifiers":3352},"Shimmi, O., Umulis, D., Othmer, H. & O'Connor, M. B. Facilitated transport of a Dpp\u002FScw heterodimer by Sog\u002FTsg leads to robust patterning of the Drosophila blastoderm embryo. Cell 120, 873–886 (2005). Evidence for an intriguing hypothesis explaining the biphasic signal required for specifying the two dorsal tissue types in D. melanogaster.",{"doi":3353},"10.1016\u002Fj.cell.2005.02.009",{"id":24,"text":3355,"url":24,"identifiers":3356},"Dubois, C. M., Laprise, M. H., Blanchette, F., Gentry, L. E. & Leduc, R. Processing of transforming growth factor β1 precursor by human furin convertase. J. Biol. Chem. 270, 10618–10624 (1995).",{"doi":3357},"10.1074\u002Fjbc.270.18.10618",{"id":24,"text":3359,"url":24,"identifiers":3360},"Constam, D. B. & Robertson, E. J. Regulation of bone morphogenetic protein activity by pro domains and proprotein convertases. J. Cell Biol. 144, 139–149 (1999).",{"doi":3361},"10.1083\u002Fjcb.144.1.139",{"id":24,"text":3363,"url":24,"identifiers":3364},"Ben-Haim, N. et al. The nodal precursor acting via activin receptors induces mesoderm by maintaining a source of its convertases and BMP4. Dev. Cell 11, 313–323 (2006).",{"doi":3365},"10.1016\u002Fj.devcel.2006.07.005",{"id":24,"text":3367,"url":24,"identifiers":3368},"Ge, G., Hopkins, D. R., Ho, W. B. & Greenspan, D. S. GDF11 forms a bone morphogenetic protein 1-activated latent complex that can modulate nerve growth factor-induced differentiation of PC12 cells. Mol. Cell. Biol. 25, 5846–5858 (2005).",{"doi":3369},"10.1128\u002FMCB.25.14.5846-5858.2005",{"id":24,"text":3371,"url":24,"identifiers":3372},"Annes, J. P., Munger, J. S. & Rifkin, D. B. Making sense of latent TGFβ activation. J. Cell Sci. 116, 217–224 (2003).",{"doi":3373},"10.1242\u002Fjcs.00229",{"id":24,"text":3375,"url":24,"identifiers":3376},"Ge, G. & Greenspan, D. S. BMP1 controls TGFβ1 activation via cleavage of latent TGFβ-binding protein. J. Cell Biol. 175, 111–120 (2006).",{"doi":3377},"10.1083\u002Fjcb.200606058",{"id":24,"text":3379,"url":24,"identifiers":3380},"Shi, Y. & Massagué, J. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 113, 685–700 (2003).",{"doi":3381},"10.1016\u002FS0092-8674(03)00432-X",{"id":24,"text":3383,"url":24,"identifiers":3384},"Yeo, C. & Whitman, M. Nodal signals to SMADs through Cripto-dependent and Cripto-independent mechanisms. Mol. Cell 7, 949–957 (2001).",{"doi":3385},"10.1016\u002FS1097-2765(01)00249-0",{"id":24,"text":3387,"url":24,"identifiers":3388},"Feng, X. H. & Derynck, R. Specificity and versatility in TGFβ signaling through SMADs. Annu. Rev. Cell Dev. Biol. 21, 659–693 (2005).",{"doi":3389},"10.1146\u002Fannurev.cellbio.21.022404.142018",{"id":24,"text":3391,"url":24,"identifiers":3392},"Allendorph, G. P., Vale, W. W. & Choe, S. Structure of the ternary signaling complex of a TGF-β superfamily member. Proc. Natl Acad. Sci. USA 103, 7643–7648 (2006). Insights into constraints for receptor assembly gained through a structure of a ternary ligand–type II–type I receptor complex.",{"doi":3393},"10.1073\u002Fpnas.0602558103",{"id":24,"text":3395,"url":24,"identifiers":3396},"Yagi, K. et al. Alternatively spliced variant of SMAD2 lacking exon 3. Comparison with wild-type SMAD2 and SMAD3. J. Biol. Chem. 274, 703–709 (1999).",{"doi":3397},"10.1074\u002Fjbc.274.2.703",{"id":24,"text":3399,"url":24,"identifiers":3400},"Sapkota, G., Alarcon, C., Spagnoli, F. M., Brivanlou, A. H. & Massagué, J. Balancing BMP signaling through integrated inputs into the SMAD1 linker. Mol. Cell 25, 441–454 (2007).",{"doi":3401},"10.1016\u002Fj.molcel.2007.01.006",{"id":24,"text":3403,"url":24,"identifiers":3404},"Liu, F. SMAD3 phosphorylation by cyclin-dependent kinases. Cytokine Growth Factor Rev. 17, 9–17 (2006).",{"doi":3405},"10.1016\u002Fj.cytogfr.2005.09.010",{"id":24,"text":3407,"url":24,"identifiers":3408},"Ross, S. et al. SMADs orchestrate specific histone modifications and chromatin remodeling to activate transcription. EMBO J. 25, 4490–4502 (2006).",{"doi":3409},"10.1038\u002Fsj.emboj.7601332",{"id":24,"text":3411,"url":24,"identifiers":3412},"Moustakas, A. & Heldin, C. H. Non-SMAD TGF-β signals. J. Cell Sci. 118, 3573–3584 (2005).",{"doi":3413},"10.1242\u002Fjcs.02554",{"id":24,"text":3415,"url":24,"identifiers":3416},"Ozdamar, B. et al. Regulation of the polarity protein Par6 by TGFβ receptors controls epithelial cell plasticity. Science 307, 1603–1609 (2005).",{"doi":3417},"10.1126\u002Fscience.1105718",{"id":24,"text":3419,"url":24,"identifiers":3420},"Lee, M. K. et al. TGF-β activates Erk MAP kinase signalling through direct phosphorylation of ShcA. EMBO J. 26, 3957–3967 (2007).",{"doi":3421},"10.1038\u002Fsj.emboj.7601818",{"id":24,"text":3423,"url":24,"identifiers":3424},"Itoh, S. & ten Dijke, P. Negative regulation of TGF-β receptor\u002FSMAD signal transduction. Curr. Opin. Cell Biol. 19, 176–184 (2007).",{"doi":3425},"10.1016\u002Fj.ceb.2007.02.015",{"id":24,"text":3427,"url":24,"identifiers":3428},"Hayashi, H. et al. The MAD-related protein SMAD7 associates with the TGFβ receptor and functions as an antagonist of TGFβ signaling. Cell 89, 1165–1173 (1997).",{"doi":3429},"10.1016\u002FS0092-8674(00)80303-7",{"id":24,"text":3431,"url":24,"identifiers":3432},"Kavsak, P. et al. SMAD7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF β receptor for degradation. Mol. Cell 6, 1365–1375 (2000).",{"doi":3433},"10.1016\u002FS1097-2765(00)00134-9",{"id":24,"text":3435,"url":24,"identifiers":3436},"Ebisawa, T. et al. Smurf1 interacts with transforming growth factor-β type I receptor through SMAD7 and induces receptor degradation. J. Biol. Chem. 276, 12477–12480 (2001).",{"doi":3437},"10.1074\u002Fjbc.C100008200",{"id":24,"text":3439,"url":24,"identifiers":3440},"Ogunjimi, A. A. et al. Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain. Mol. Cell 19, 297–308 (2005).",{"doi":3441},"10.1016\u002Fj.molcel.2005.06.028",{"id":24,"text":3443,"url":24,"identifiers":3444},"Shi, W. et al. GADD34–PP1c recruited by SMAD7 dephosphorylates TGFβ type I receptor. J. Cell Biol. 164, 291–300 (2004).",{"doi":3445},"10.1083\u002Fjcb.200307151",{"id":24,"text":3447,"url":24,"identifiers":3448},"Zhang, S. et al. SMAD7 antagonizes transforming growth factor β signaling in the nucleus by interfering with functional SMAD–DNA complex formation. Mol. Cell. Biol. 27, 4488–4499 (2007).",{"doi":3449},"10.1128\u002FMCB.01636-06",{"id":24,"text":3451,"url":24,"identifiers":3452},"Macias-Silva, M., Hoodless, P. A., Tang, S. J., Buchwald, M. & Wrana, J. L. Specific activation of SMAD1 signaling pathways by the BMP7 type I receptor, ALK2. J. Biol. Chem. 273, 25628–25636 (1998).",{"doi":3453},"10.1074\u002Fjbc.273.40.25628",{"id":24,"text":3455,"url":24,"identifiers":3456},"Sakuma, R. et al. Inhibition of Nodal signalling by Lefty mediated through interaction with common receptors and efficient diffusion. Genes Cells 7, 401–412 (2002).",{"doi":3457},"10.1046\u002Fj.1365-2443.2002.00528.x",{"id":24,"text":3459,"url":24,"identifiers":3460},"Greenwald, J. et al. The BMP7\u002FActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly. Mol. Cell 11, 605–617 (2003).",{"doi":3461},"10.1016\u002FS1097-2765(03)00094-7",{"id":24,"text":3463,"url":24,"identifiers":3464},"Rebbapragada, A., Benchabane, H., Wrana, J. L., Celeste, A. J. & Attisano, L. Myostatin signals through a transforming growth factor β-like signaling pathway to block adipogenesis. Mol. Cell. Biol. 23, 7230–7242 (2003).",{"doi":3465},"10.1128\u002FMCB.23.20.7230-7242.2003",{"id":24,"text":3467,"url":24,"identifiers":3468},"Andersson, O., Reissmann, E. & Ibanez, C. F. Growth differentiation factor 11 signals through the transforming growth factor-β receptor ALK5 to regionalize the anterior–posterior axis. EMBO Rep. 7, 831–837 (2006).",{"doi":3469},"10.1038\u002Fsj.embor.7400752",{"id":24,"text":3471,"url":24,"identifiers":3472},"Oh, S. P. et al. Activin type IIA and IIB receptors mediate Gdf11 signaling in axial vertebral patterning. Genes Dev. 16, 2749–2754 (2002).",{"doi":3473},"10.1101\u002Fgad.1021802",{"id":24,"text":3475,"url":24,"identifiers":3476},"Balemans, W. & Van Hul, W. Extracellular regulation of BMP signaling in vertebrates: a cocktail of modulators. Dev. Biol. 250, 231–250 (2002).",{"doi":3477},"10.1006\u002Fdbio.2002.0779",{"id":24,"text":3479,"url":24,"identifiers":3480},"Piccolo, S. et al. The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals. Nature 397, 707–710 (1999).",{"doi":3481},"10.1038\u002F17820",{"id":24,"text":3483,"url":24,"identifiers":3484},"Hemmati-Brivanlou, A., Kelly, O. G. & Melton, D. A. Follistatin, an antagonist of activin, is expressed in the Spemann organizer and displays direct neuralizing activity. Cell 77, 283–295 (1994).",{"doi":3485},"10.1016\u002F0092-8674(94)90320-4",{"id":24,"text":3487,"url":24,"identifiers":3488},"Thompson, T. B., Lerch, T. F., Cook, R. W., Woodruff, T. K. & Jardetzky, T. S. The structure of the follistatin:activin complex reveals antagonism of both type I and type II receptor binding. Dev. Cell 9, 535–543 (2005).",{"doi":3489},"10.1016\u002Fj.devcel.2005.09.008",{"id":24,"text":3491,"url":24,"identifiers":3492},"Schier, A. F. Nodal signaling in vertebrate development. Annu. Rev. Cell Dev. Biol. 19, 589–621 (2003).",{"doi":3493},"10.1146\u002Fannurev.cellbio.19.041603.094522",{"id":24,"text":3495,"url":24,"identifiers":3496},"Cheng, S. K., Olale, F., Brivanlou, A. H. & Schier, A. F. Lefty blocks a subset of TGFβ signals by antagonizing EGF-CFC coreceptors. PLoS Biol. 2, e30 (2004).",{"doi":3497},"10.1371\u002Fjournal.pbio.0020030",{"id":24,"text":3499,"url":24,"identifiers":3500},"Chen, Y. G. et al. Determinants of specificity in TGF-β signal transduction. Genes Dev. 12, 2144–2152 (1998).",{"doi":3501},"10.1101\u002Fgad.12.14.2144",{"id":24,"text":3503,"url":24,"identifiers":3504},"Miyazawa, K., Shinozaki, M., Hara, T., Furuya, T. & Miyazono, K. Two major SMAD pathways in TGF-β superfamily signalling. Genes Cells 7, 1191–1204 (2002).",{"doi":3505},"10.1046\u002Fj.1365-2443.2002.00599.x",{"id":24,"text":3507,"url":24,"identifiers":3508},"Gilchrist, R. B. et al. Molecular basis of oocyte–paracrine signalling that promotes granulosa cell proliferation. J. Cell Sci. 119, 3811–3821 (2006).",{"doi":3509},"10.1242\u002Fjcs.03105",{"id":24,"text":3511,"url":24,"identifiers":3512},"Goumans, M. J. et al. Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFβ\u002FALK5 signaling. Mol. Cell 12, 817–828 (2003). Evidence for the formation of receptor complexes that contain both ALK1 and ALK5 and activate both subclasses of R-SMADs in response to a single ligand, TGFβ.",{"doi":3513},"10.1016\u002FS1097-2765(03)00386-1",{"id":24,"text":3515,"url":24,"identifiers":3516},"Goumans, M. J. et al. Balancing the activation state of the endothelium via two distinct TGF-β type I receptors. EMBO J. 21, 1743–1753 (2002).",{"doi":3517},"10.1093\u002Femboj\u002F21.7.1743",{"id":24,"text":3519,"url":24,"identifiers":3520},"Byfield, S. D. & Roberts, A. B. Lateral signaling enhances TGF-β response complexity. Trends Cell Biol. 14, 107–111 (2004).",{"doi":3521},"10.1016\u002Fj.tcb.2004.01.001",{"id":24,"text":3523,"url":24,"identifiers":3524},"Batut, J., Howell, M. & Hill, C. S. Kinesin-mediated transport of SMAD2 is required for signaling in response to TGF-β ligands. Dev. Cell 12, 261–274 (2007). A requirement for intact microtubules and the motor protein kinesin-1 for efficient SMAD2 phosphorylation suggests a sophisticated mechanism that presents SMADs to receptors.",{"doi":3525},"10.1016\u002Fj.devcel.2007.01.010",{"id":24,"text":3527,"url":24,"identifiers":3528},"Shi, W. et al. Endofin acts as a SMAD anchor for receptor activation in BMP signaling. J. Cell Sci. 120, 1216–1224 (2007).",{"doi":3529},"10.1242\u002Fjcs.03400",{"id":24,"text":3531,"url":24,"identifiers":3532},"Chen, Y. G., Wang, Z., Ma, J., Zhang, L. & Lu, Z. Endofin, a FYVE domain protein, interacts with SMAD4 and facilitates transforming growth factor-β signaling. J. Biol. Chem. 282, 9688–9695 (2007).",{"doi":3533},"10.1074\u002Fjbc.M611704200",{"id":24,"text":3535,"url":24,"identifiers":3536},"Massagué, J., Seoane, J. & Wotton, D. SMAD transcription factors. Genes Dev. 19, 2783–2810 (2005).",{"doi":3537},"10.1101\u002Fgad.1350705",{"id":24,"text":3539,"url":24,"identifiers":3540},"Dennler, S. et al. Direct binding of SMAD3 and SMAD4 to critical TGF β-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene. EMBO J. 17, 3091–3100 (1998).",{"doi":3541},"10.1093\u002Femboj\u002F17.11.3091",{"id":24,"text":3543,"url":24,"identifiers":3544},"Zawel, L. et al. Human SMAD3 and SMAD4 are sequence-specific transcription activators. Mol. Cell 1, 611–617 (1998).",{"doi":3545},"10.1016\u002FS1097-2765(00)80061-1",{"id":24,"text":3547,"url":24,"identifiers":3548},"Shi, Y. et al. Crystal structure of a SMAD MH1 domain bound to DNA: insights on DNA binding in TGF-β signaling. Cell 94, 585–594 (1998).",{"doi":3549},"10.1016\u002FS0092-8674(00)81600-1",{"id":24,"text":3551,"url":24,"identifiers":3552},"Kim, J., Johnson, K., Chen, H. J., Carroll, S. & Laughon, A. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. Nature 388, 304–308 (1997). Identification of the first SBE.",{"doi":3553},"10.1038\u002F40906",{"id":24,"text":3555,"url":24,"identifiers":3556},"Gao, S., Steffen, J. & Laughon, A. Dpp-responsive silencers are bound by a trimeric Mad–Medea complex. J. Biol. Chem. 280, 36158–36164 (2005).",{"doi":3557},"10.1074\u002Fjbc.M506882200",{"id":24,"text":3559,"url":24,"identifiers":3560},"Pyrowolakis, G., Hartmann, B., Muller, B., Basler, K. & Affolter, M. A simple molecular complex mediates widespread BMP-induced repression during Drosophila development. Dev. Cell 7, 229–240 (2004). Identification of the MAD–Medea–Schnurri repressor complex.",{"doi":3561},"10.1016\u002Fj.devcel.2004.07.008",{"id":24,"text":3563,"url":24,"identifiers":3564},"Yao, L. C. et al. Schnurri transcription factors from Drosophila and vertebrates can mediate Bmp signaling through a phylogenetically conserved mechanism. Development 133, 4025–4034 (2006). D. melanogaster Schnurri and its vertebrate homologue are functionally equivalent: both bind BMP-responsive elements together with SMAD1 and SMAD4 (MAD and Medea). Interestingly, in a D. melanogaster context, this causes target-gene repression, but causes target-gene activation in a vertebrate context.",{"doi":3565},"10.1242\u002Fdev.02561",{"id":24,"text":3567,"url":24,"identifiers":3568},"Korchynskyi, O. & ten Dijke, P. Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter. J. Biol. Chem. 277, 4883–4891 (2002).",{"doi":3569},"10.1074\u002Fjbc.M111023200",{"id":24,"text":3571,"url":24,"identifiers":3572},"Stroschein, S. L., Wang, W., Zhou, S., Zhou, Q. & Luo, K. Negative feedback regulation of TGF-β signaling by the SnoN oncoprotein. Science 286, 771–774 (1999).",{"doi":3573},"10.1126\u002Fscience.286.5440.771",{"id":24,"text":3575,"url":24,"identifiers":3576},"Levy, L. et al. Arkadia activates SMAD3\u002FSMAD4-dependent transcription by triggering signal-induced SnoN degradation. Mol. Cell. Biol. 27, 6068–6083 (2007). The E3-ubiquitin ligase Arkadia is absolutely required for SMAD3-dependent gene activation from SNON-repressed promoters by inducing degradation of SNON in response to TGFβ.",{"doi":3577},"10.1128\u002FMCB.00664-07",{"id":24,"text":3579,"url":24,"identifiers":3580},"Nagano, Y. et al. Arkadia induces degradation of SnoN and c-Ski to enhance TGF-β signaling. J. Biol. Chem. 282, 20492–20501 (2007).",{"doi":3581},"10.1074\u002Fjbc.M701294200",{"id":24,"text":3583,"url":24,"identifiers":3584},"Chen, X., Rubock, M. J. & Whitman, M. A transcriptional partner for MAD proteins in TGF-β signalling. Nature 383, 691–696 (1996).",{"doi":3585},"10.1038\u002F383691a0",{"id":24,"text":3587,"url":24,"identifiers":3588},"Chen, X. et al. SMAD4 and FAST-1 in the assembly of activin-responsive factor. Nature 389, 85–89 (1997).",{"doi":3589},"10.1038\u002F38008",{"id":24,"text":3591,"url":24,"identifiers":3592},"Germain, S., Howell, M., Esslemont, G. M. & Hill, C. S. Homeodomain and winged-helix transcription factors recruit activated SMADs to distinct promoter elements via a common SMAD interaction motif. Genes Dev. 14, 435–451 (2000).",{"doi":3593},"10.1101\u002Fgad.14.4.435",{"id":24,"text":3595,"url":24,"identifiers":3596},"Kunwar, P. S. et al. Mixer\u002FBon and FoxH1\u002FSur have overlapping and divergent roles in Nodal signaling and mesendoderm induction. Development 130, 5589–5599 (2003).",{"doi":3597},"10.1242\u002Fdev.00803",{"id":24,"text":3599,"url":24,"identifiers":3600},"Randall, R. A., Germain, S., Inman, G. J., Bates, P. A. & Hill, C. S. Different SMAD2 partners bind a common hydrophobic pocket in SMAD2 via a defined proline-rich motif. EMBO J. 21, 145–156 (2002).",{"doi":3601},"10.1093\u002Femboj\u002F21.1.145",{"id":24,"text":3603,"url":24,"identifiers":3604},"Kang, Y., Chen, C. R. & Massagué, J. A self-enabling TGFβ response coupled to stress signaling: SMAD engages stress response factor ATF3 for Id1 repression in epithelial cells. Mol. Cell 11, 915–926 (2003).",{"doi":3605},"10.1016\u002FS1097-2765(03)00109-6",{"id":24,"text":3607,"url":24,"identifiers":3608},"Cordenonsi, M. et al. Integration of TGF-β and Ras\u002FMAPK signaling through p53 phosphorylation. Science 315, 840–843 (2007). p53 enables crosstalk between receptor tyrosine kinase signalling and TGFβ signalling.",{"doi":3609},"10.1126\u002Fscience.1135961",{"id":24,"text":3611,"url":24,"identifiers":3612},"He, W. et al. Hematopoiesis controlled by distinct TIF1γ and SMAD4 branches of the TGFβ pathway. Cell 125, 929–941 (2006). Proposes a mechanism by which ectodermin (also known as TIF1γ or TRIM33) can compete with SMAD4 for SMAD2\u002F3 binding, thus forming an alternative transcriptionally active complex.",{"doi":3613},"10.1016\u002Fj.cell.2006.03.045",{"id":24,"text":3615,"url":24,"identifiers":3616},"Dupont, S. et al. Germ-layer specification and control of cell growth by Ectodermin, a SMAD4 ubiquitin ligase. Cell 121, 87–99 (2005). Ectodermin is shown to restrict TGFβ signalling by acting as a RING-domain ubiquitin ligase that targets SMAD4 for degradation.",{"doi":3617},"10.1016\u002Fj.cell.2005.01.033",{"id":24,"text":3619,"url":24,"identifiers":3620},"Gurdon, J. B., Dyson, S. & St Johnston, D. Cells' perception of position in a concentration gradient. Cell 95, 159–162 (1998).",{"doi":3621},"10.1016\u002FS0092-8674(00)81747-X",{"id":24,"text":3623,"url":24,"identifiers":3624},"Green, J. B. & Smith, J. C. Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate. Nature 347, 391–394 (1990).",{"doi":3625},"10.1038\u002F347391a0",{"id":24,"text":3627,"url":24,"identifiers":3628},"Dyson, S. & Gurdon, J. B. The interpretation of position in a morphogen gradient as revealed by occupancy of activin receptors. Cell 93, 557–568 (1998).",{"doi":3629},"10.1016\u002FS0092-8674(00)81185-X",{"id":24,"text":3631,"url":24,"identifiers":3632},"Inman, G. J. et al. SB-431542 is a potent and specific inhibitor of transforming growth factor-β superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol. Pharmacol. 62, 65–74 (2002).",{"doi":3633},"10.1124\u002Fmol.62.1.65",{"id":24,"text":3635,"url":24,"identifiers":3636},"Jullien, J. & Gurdon, J. Morphogen gradient interpretation by a regulated trafficking step during ligand-receptor transduction. Genes Dev. 19, 2682–2694 (2005).",{"doi":3637},"10.1101\u002Fgad.341605",{"id":24,"text":3639,"url":24,"identifiers":3640},"Raftery, L. A. & Sutherland, D. J. Gradients and thresholds: BMP response gradients unveiled in Drosophila embryos. Trends Genet. 19, 701–708 (2003).",{"doi":3641},"10.1016\u002Fj.tig.2003.10.009",{"id":24,"text":3643,"url":24,"identifiers":3644},"Lee, M. A., Heasman, J. & Whitman, M. Timing of endogenous activin-like signals and regional specification of the Xenopus embryo. Development 128, 2939–2952 (2001).",{"doi":3645},"10.1242\u002Fdev.128.15.2939",{"id":24,"text":3647,"url":24,"identifiers":3648},"Di Guglielmo, G. M., Le Roy, C., Goodfellow, A. F. & Wrana, J. L. Distinct endocytic pathways regulate TGF-β receptor signalling and turnover. Nature Cell Biol. 5, 410–421 (2003). Introduces the concept of two distinct competing endocytic routes for TGFβ receptors.",{"doi":3649},"10.1038\u002Fncb975",{"id":24,"text":3651,"url":24,"identifiers":3652},"Le Roy, C. & Wrana, J. L. Clathrin- and non-clathrin-mediated endocytic regulation of cell signalling. Nature Rev. Mol. Cell Biol. 6, 112–126 (2005).",{"doi":3653},"10.1038\u002Fnrm1571",{"id":24,"text":3655,"url":24,"identifiers":3656},"Inman, G. J., Nicolás, F. J. & Hill, C. S. Nucleocytoplasmic shuttling of SMADs 2, 3, and 4 permits sensing of TGF-β receptor activity. Mol. Cell 10, 283–294 (2002).",{"doi":3657},"10.1016\u002FS1097-2765(02)00585-3",{"id":24,"text":3659,"url":24,"identifiers":3660},"Nicolás, F. J., De Bosscher, K., Schmierer, B. & Hill, C. S. Analysis of SMAD nucleocytoplasmic shuttling in living cells. J. Cell Sci. 117, 4113–4125 (2004).",{"doi":3661},"10.1242\u002Fjcs.01289",{"id":24,"text":3663,"url":24,"identifiers":3664},"Schmierer, B. & Hill, C. S. Kinetic analysis of SMAD nucleocytoplasmic shuttling reveals a mechanism for transforming growth factor β-dependent nuclear accumulation of SMADs. Mol. Cell. Biol. 25, 9845–9858 (2005).",{"doi":3665},"10.1128\u002FMCB.25.22.9845-9858.2005",{"id":24,"text":3667,"url":24,"identifiers":3668},"Lo, R. S. & Massagué, J. Ubiquitin-dependent degradation of TGF-β-activated SMAD2. Nature Cell Biol. 1, 472–478 (1999).",{"doi":3669},"10.1038\u002F70258",{"id":24,"text":3671,"url":24,"identifiers":3672},"Xu, L. & Massagué, J. Nucleocytoplasmic shuttling of signal transducers. Nature Rev. Mol. Cell Biol. 5, 209–219 (2004).",{"doi":3673},"10.1038\u002Fnrm1331",{"id":24,"text":3675,"url":24,"identifiers":3676},"Chen, H. B., Shen, J., Ip, Y. T. & Xu, L. Identification of phosphatases for SMAD in the BMP\u002FDPP pathway. Genes Dev. 20, 648–653 (2006).",{"doi":3677},"10.1101\u002Fgad.1384706",{"id":24,"text":3679,"url":24,"identifiers":3680},"Lin, X. et al. PPM1A functions as a SMAD phosphatase to terminate TGFβ signaling. Cell 125, 915–928 (2006). Convincingly establishes PPM1A as an R-SMAD C-terminal phosphatase.",{"doi":3681},"10.1016\u002Fj.cell.2006.03.044",{"id":24,"text":3683,"url":24,"identifiers":3684},"Duan, X., Liang, Y. Y., Feng, X. H. & Lin, X. Dephosphorylation of SMAD1 in the BMP signaling pathway by PPM1A. J. Biol. Chem. 281, 36526–36532 (2006).",{"doi":3685},"10.1074\u002Fjbc.M605169200",{"id":24,"text":3687,"url":24,"identifiers":3688},"Yoshizaki, T. et al. Protein phosphatase-2C α as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. J. Biol. Chem. 279, 22715–22726 (2004).",{"doi":3689},"10.1074\u002Fjbc.M313745200",{"id":24,"text":3691,"url":24,"identifiers":3692},"Strovel, E. T., Wu, D. & Sussman, D. J. Protein phosphatase 2Cα dephosphorylates axin and activates LEF-1-dependent transcription. J. Biol. Chem. 275, 2399–2403 (2000).",{"doi":3693},"10.1074\u002Fjbc.275.4.2399",{"id":24,"text":3695,"url":24,"identifiers":3696},"Cheng, A., Kaldis, P. & Solomon, M. J. Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C α and β2 isoforms. J. Biol. Chem. 275, 34744–34749 (2000).",{"doi":3697},"10.1074\u002Fjbc.M006210200",{"id":24,"text":3699,"url":24,"identifiers":3700},"Pierreux, C. E., Nicolás, F. J. & Hill, C. S. Transforming growth factor β-independent shuttling of SMAD4 between the cytoplasm and nucleus. Mol. Cell. Biol. 20, 9041–9054 (2000).",{"doi":3701},"10.1128\u002FMCB.20.23.9041-9054.2000",{"id":24,"text":3703,"url":24,"identifiers":3704},"Xu, L., Kang, Y., Col, S. & Massagué, J. SMAD2 nucleocytoplasmic shuttling by nucleoporins CAN\u002FNup214 and Nup153 feeds TGFβ signaling complexes in the cytoplasm and nucleus. Mol. Cell 10, 271–282 (2002).",{"doi":3705},"10.1016\u002FS1097-2765(02)00586-5",{"id":24,"text":3707,"url":24,"identifiers":3708},"Dudu, V. et al. Postsynaptic MAD signaling at the Drosophila neuromuscular junction. Curr. Biol. 16, 625–635 (2006).",{"doi":3709},"10.1016\u002Fj.cub.2006.02.061",{"id":24,"text":3711,"url":24,"identifiers":3712},"Chen, H. B., Rud, J. G., Lin, K. & Xu, L. Nuclear targeting of transforming growth factor-β-activated SMAD complexes. J. Biol. Chem. 280, 21329–21336 (2005).",{"doi":3713},"10.1074\u002Fjbc.M500362200",{"id":24,"text":3715,"url":24,"identifiers":3716},"Kolch, W. Meaningful relationships: the regulation of the Ras\u002FRaf\u002FMEK\u002FERK pathway by protein interactions. Biochem. J. 351, 289–305 (2000).",{"doi":3717},"10.1042\u002Fbj3510289",{"id":24,"text":3719,"url":24,"identifiers":3720},"Schoeberl, B., Eichler-Jonsson, C., Gilles, E. D. & Muller, G. Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors. Nature Biotechnol. 20, 370–375 (2002).",{"doi":3721},"10.1038\u002Fnbt0402-370",{"id":24,"text":3723,"url":24,"identifiers":3724},"Podos, S. D., Hanson, K. K., Wang, Y. C. & Ferguson, E. L. The DSmurf ubiquitin-protein ligase restricts BMP signaling spatially and temporally during Drosophila embryogenesis. Dev. Cell 1, 567–578 (2001).",{"doi":3725},"10.1016\u002FS1534-5807(01)00057-0",{"id":24,"text":3727,"url":24,"identifiers":3728},"Turing, A. The chemical basis of morphogenesis. Phil. Trans. R. Soc. Lond. B 237, 37–72 (1952).",{"doi":3729},"10.1098\u002Frstb.1952.0012",{"id":24,"text":3731,"url":24,"identifiers":3732},"Meinhardt, H. Models for positional signalling with application to the dorsoventral patterning of insects and segregation into different cell types. Development 107 Suppl., 169–180 (1989).",{"doi":3733},"10.1242\u002Fdev.107.Supplement.169",{"id":24,"text":3735,"url":24,"identifiers":3736},"Piccolo, S. et al. Cleavage of Chordin by Xolloid metalloprotease suggests a role for proteolytic processing in the regulation of Spemann organizer activity. Cell 91, 407–416 (1997).",{"doi":3737},"10.1016\u002FS0092-8674(00)80424-9",{"id":24,"text":3739,"url":24,"identifiers":3740},"Hopkins, D. R., Keles, S. & Greenspan, D. S. The bone morphogenetic protein 1\u002FTolloid-like metalloproteinases. Matrix Biol. 26, 508–523 (2007).",{"doi":3741},"10.1016\u002Fj.matbio.2007.05.004",{"id":24,"text":3743,"url":24,"identifiers":3744},"Lee, H. X., Ambrosio, A. L., Reversade, B. & De Robertis, E. M. Embryonic dorsal-ventral signaling: secreted frizzled-related proteins as inhibitors of tolloid proteinases. Cell 124, 147–159 (2006).",{"doi":3745},"10.1016\u002Fj.cell.2005.12.018",{"id":24,"text":3747,"url":24,"identifiers":3748},"Muraoka, O. et al. Sizzled controls dorso-ventral polarity by repressing cleavage of the Chordin protein. Nature Cell Biol. 8, 329–338 (2006).",{"doi":3749},"10.1038\u002Fncb1379",{"id":24,"text":3751,"url":24,"identifiers":3752},"Reeves, G. T., Muratov, C. B., Schupbach, T. & Shvartsman, S. Y. Quantitative models of developmental pattern formation. Dev. Cell 11, 289–300 (2006).",{"doi":3753},"10.1016\u002Fj.devcel.2006.08.006",{"id":24,"text":3755,"url":24,"identifiers":3756},"Teleman, A. A., Strigini, M. & Cohen, S. M. Shaping morphogen gradients. Cell 105, 559–562 (2001).",{"doi":3757},"10.1016\u002FS0092-8674(01)00377-4",{"id":24,"text":3759,"url":24,"identifiers":3760},"Freeman, M. & Gurdon, J. B. Regulatory principles of developmental signaling. Annu. Rev. Cell Dev. Biol. 18, 515–539 (2002).",{"doi":3761},"10.1146\u002Fannurev.cellbio.18.012502.083458",{"id":24,"text":3763,"url":24,"identifiers":3764},"Lander, A. D. Morpheus unbound: reimagining the morphogen gradient. Cell 128, 245–256 (2007).",{"doi":3765},"10.1016\u002Fj.cell.2007.01.004",{"id":24,"text":3767,"url":24,"identifiers":3768},"Ferguson, E. L. & Anderson, K. V. Decapentaplegic acts as a morphogen to organize dorsal–ventral pattern in the Drosophila embryo. Cell 71, 451–461 (1992).",{"doi":3769},"10.1016\u002F0092-8674(92)90514-D",{"id":24,"text":3771,"url":24,"identifiers":3772},"Nellen, D., Burke, R., Struhl, G. & Basler, K. Direct and long-range action of a DPP morphogen gradient. Cell 85, 357–368 (1996).",{"doi":3773},"10.1016\u002FS0092-8674(00)81114-9",{"id":24,"text":3775,"url":24,"identifiers":3776},"Arora, K., Levine, M. S. & O'Connor, M. B. The screw gene encodes a ubiquitously expressed member of the TGF-β family required for specification of dorsal cell fates in the Drosophila embryo. Genes Dev. 8, 2588–2601 (1994).",{"doi":3777},"10.1101\u002Fgad.8.21.2588",{"id":24,"text":3779,"url":24,"identifiers":3780},"Neul, J. L. & Ferguson, E. L. Spatially restricted activation of the SAX receptor by SCW modulates DPP\u002FTKV signaling in Drosophila dorsal–ventral patterning. Cell 95, 483–494 (1998).",{"doi":3781},"10.1016\u002FS0092-8674(00)81616-5",{"id":24,"text":3783,"url":24,"identifiers":3784},"Sutherland, D. J., Li, M., Liu, X. Q., Stefancsik, R. & Raftery, L. A. Stepwise formation of a SMAD activity gradient during dorsal–ventral patterning of the Drosophila embryo. Development 130, 5705–5716 (2003).",{"doi":3785},"10.1242\u002Fdev.00801",{"id":24,"text":3787,"url":24,"identifiers":3788},"Wang, Y. C. & Ferguson, E. L. Spatial bistability of Dpp-receptor interactions during Drosophila dorsal–ventral patterning. Nature 434, 229–234 (2005).",{"doi":3789},"10.1038\u002Fnature03318",{"id":24,"text":3791,"url":24,"identifiers":3792},"Blader, P., Rastegar, S., Fischer, N. & Strahle, U. Cleavage of the BMP-4 antagonist chordin by zebrafish tolloid. Science 278, 1937–1940 (1997).",{"doi":3793},"10.1126\u002Fscience.278.5345.1937",{"id":24,"text":3795,"url":24,"identifiers":3796},"Marques, G. et al. Production of a DPP activity gradient in the early Drosophila embryo through the opposing actions of the SOG and TLD proteins. Cell 91, 417–426 (1997).",{"doi":3797},"10.1016\u002FS0092-8674(00)80425-0",{"id":24,"text":3799,"url":24,"identifiers":3800},"Mullins, M. C. Holy Tolloido: Tolloid cleaves SOG\u002FChordin to free DPP\u002FBMPs. Trends Genet. 14, 127–129 (1998).",{"doi":3801},"10.1016\u002FS0168-9525(98)01431-0",{"id":24,"text":3803,"url":24,"identifiers":3804},"Xu, L., Alarcon, C., Col, S. & Massagué, J. Distinct domain utilization by SMAD3 and SMAD4 for nucleoporin interaction and nuclear import. J. Biol. Chem. 278, 42569–42577 (2003).",{"doi":3805},"10.1074\u002Fjbc.M307601200",{"id":24,"text":3807,"url":24,"identifiers":3808},"Kurisaki, A., Kose, S., Yoneda, Y., Heldin, C. H. & Moustakas, A. Transforming growth factor-β induces nuclear import of SMAD3 in an importin-β1 and Ran-dependent manner. Mol. Biol. Cell 12, 1079–1091 (2001).",{"doi":3809},"10.1091\u002Fmbc.12.4.1079",{"id":24,"text":3811,"url":24,"identifiers":3812},"Xiao, Z., Liu, X. & Lodish, H. F. Importin β mediates nuclear translocation of SMAD 3. J. Biol. Chem. 275, 23425–23428 (2000).",{"doi":3813},"10.1074\u002Fjbc.C000345200",{"id":24,"text":3815,"url":24,"identifiers":3816},"Xiao, Z., Watson, N., Rodriguez, C. & Lodish, H. F. Nucleocytoplasmic shuttling of SMAD1 conferred by its nuclear localization and nuclear export signals. J. Biol. Chem. 276, 39404–39410 (2001).",{"doi":3817},"10.1074\u002Fjbc.M103117200",{"id":24,"text":3819,"url":24,"identifiers":3820},"Xiao, Z., Latek, R. & Lodish, H. F. An extended bipartite nuclear localization signal in SMAD4 is required for its nuclear import and transcriptional activity. Oncogene 22, 1057–1069 (2003).",{"doi":3821},"10.1038\u002Fsj.onc.1206212",{"id":24,"text":3823,"url":24,"identifiers":3824},"Xu, L. et al. Msk is required for nuclear import of TGF-β\u002FBMP-activated SMADs. J. Cell Biol. 178, 981–994 (2007).",{"doi":3825},"10.1083\u002Fjcb.200703106",{"id":24,"text":3827,"url":24,"identifiers":3828},"Watanabe, M., Masuyama, N., Fukuda, M. & Nishida, E. Regulation of intracellular dynamics of SMAD4 by its leucine-rich nuclear export signal. EMBO Rep. 1, 176–182 (2000).",{"doi":3829},"10.1093\u002Fembo-reports\u002Fkvd029",{"id":24,"text":3831,"url":24,"identifiers":3832},"Masuyama, N., Hanafusa, H., Kusakabe, M., Shibuya, H. & Nishida, E. Identification of two SMAD4 proteins in Xenopus. Their common and distinct properties. J. Biol. Chem. 274, 12163–12170 (1999).",{"doi":3833},"10.1074\u002Fjbc.274.17.12163",{"id":24,"text":3835,"url":24,"identifiers":3836},"Kurisaki, A. et al. The mechanism of nuclear export of SMAD3 involves exportin 4 and Ran. Mol. Cell. Biol. 26, 1318–1332 (2006).",{"doi":3837},"10.1128\u002FMCB.26.4.1318-1332.2006",{"id":24,"text":3839,"url":24,"identifiers":3840},"Ashe, H. L. & Briscoe, J. The interpretation of morphogen gradients. Development 133, 385–394 (2006).",{"doi":3841},"10.1242\u002Fdev.02238",{"id":24,"text":3843,"url":24,"identifiers":3844},"Randall, R. A. et al. Recognition of phosphorylated-SMAD2-containing complexes by a novel SMAD interaction motif. Mol. Cell. Biol. 24, 1106–1121 (2004).",{"doi":3845},"10.1128\u002FMCB.24.3.1106-1121.2004",{"id":24,"text":3847,"url":24,"identifiers":3848},"Wharton, S. J., Basu, S. P. & Ashe, H. L. SMAD affinity can direct distinct readouts of the embryonic extracellular Dpp gradient in Drosophila. Curr. Biol. 14, 1550–1558 (2004).",{"doi":3849},"10.1016\u002Fj.cub.2004.08.053",{"id":24,"text":3851,"url":24,"identifiers":3852},"Saka, Y. & Smith, J. C. A mechanism for the sharp transition of morphogen gradient interpretation in Xenopus. BMC Dev. Biol. 7, 47 (2007).",{"doi":3853},"10.1186\u002F1471-213X-7-47",{"id":24,"text":3855,"url":24,"identifiers":3856},"Latinkic, B. V. et al. The Xenopus Brachyury promoter is activated by FGF and low concentrations of activin and suppressed by high concentrations of activin and by paired-type homeodomain proteins. Genes Dev. 11, 3265–3276 (1997).",{"doi":3857},"10.1101\u002Fgad.11.23.3265",{"id":24,"text":3859,"url":24,"identifiers":3860},"Green, J. B., New, H. V. & Smith, J. C. Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm. Cell 71, 731–739 (1992).",{"doi":3861},"10.1016\u002F0092-8674(92)90550-V",{"id":24,"text":3863,"url":24,"identifiers":3864},"Ladher, R., Mohun, T. J., Smith, J. C. & Snape, A. M. Xom: a Xenopus homeobox gene that mediates the early effects of BMP-4. Development 122, 2385–2394 (1996).",{"doi":3865},"10.1242\u002Fdev.122.8.2385",{"id":24,"text":3867,"url":24,"identifiers":3868},"Trindade, M., Tada, M. & Smith, J. C. DNA-binding specificity and embryological function of Xom (Xvent-2). Dev. Biol. 216, 442–456 (1999).",{"doi":3869},"10.1006\u002Fdbio.1999.9507",{"id":24,"text":3871,"url":24,"identifiers":3872},"Messenger, N. J. et al. Functional specificity of the Xenopus T-domain protein Brachyury is conferred by its ability to interact with SMAD1. Dev. Cell 8, 599–610 (2005).",{"doi":3873},"10.1016\u002Fj.devcel.2005.03.001",{"id":24,"text":3875,"url":24,"identifiers":3876},"Artinger, M., Blitz, I., Inoue, K., Tran, U. & Cho, K. W. Interaction of goosecoid and brachyury in Xenopus mesoderm patterning. Mech. Dev. 65, 187–196 (1997).",{"doi":3877},"10.1016\u002FS0925-4773(97)00073-7",{"id":24,"text":3879,"url":24,"identifiers":3880},"Arora, K. et al. The Drosophila schnurri gene acts in the Dpp\u002FTGF β signaling pathway and encodes a transcription factor homologous to the human MBP family. Cell 81, 781–790 (1995).",{"doi":3881},"10.1016\u002F0092-8674(95)90539-1",{"id":24,"text":3883,"url":24,"identifiers":3884},"Grieder, N. C., Nellen, D., Burke, R., Basler, K. & Affolter, M. Schnurri is required for Drosophila Dpp signaling and encodes a zinc finger protein similar to the mammalian transcription factor PRDII-BF1. Cell 81, 791–800 (1995).",{"doi":3885},"10.1016\u002F0092-8674(95)90540-5",{"id":24,"text":3887,"url":24,"identifiers":3888},"Muller, B., Hartmann, B., Pyrowolakis, G., Affolter, M. & Basler, K. Conversion of an extracellular Dpp\u002FBMP morphogen gradient into an inverse transcriptional gradient. Cell 113, 221–233 (2003). Establishes the concept of a repressive Brinker gradient that is reciprocal to a DPP gradient.",{"doi":3889},"10.1016\u002FS0092-8674(03)00241-1",{"id":24,"text":3891,"url":24,"identifiers":3892},"Affolter, M., Marty, T., Vigano, M. A. & Jazwinska, A. Nuclear interpretation of Dpp signaling in Drosophila. EMBO J. 20, 3298–3305 (2001).",{"doi":3893},"10.1093\u002Femboj\u002F20.13.3298",{"id":24,"text":3895,"url":24,"identifiers":3896},"Barrio, R. & de Celis, J. F. Regulation of spalt expression in the Drosophila wing blade in response to the Decapentaplegic signaling pathway. Proc. Natl Acad. Sci. USA 101, 6021–6026 (2004).",{"doi":3897},"10.1073\u002Fpnas.0401590101",{"id":24,"text":3899,"url":24,"identifiers":3900},"Chenna, R. et al. Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res. 31, 3497–3500 (2003).",{"doi":3901},"10.1093\u002Fnar\u002Fgkg500",{"id":3903,"createTime":3904,"updateTime":3904,"relativeEntities":3905,"slug":3906,"properties":3907,"entityType":131,"verifyStatus":132,"verifyTime":3917,"verifyNote":133,"languages":3918,"translateLanguages":24,"viewCount":25,"primaryUrl":3919,"fullTextUrl":24,"authors":3920,"publicationType":174,"publisherRelationship":3959,"citationCount":4013,"citationInfo":4014,"publishDate":4021,"publishYear":531,"citationAnalyzeStatus":23,"lastCitationAnalyze":24,"indexDatabases":4022,"openAccess":24,"references":4023,"isForceReanalyzing":409},"f187819f-c73b-4956-a968-db07193e8caa","2025-02-09T14:29:14.758+00:00",[],"Clathrin-and-non-clathrin-mediated-endocytic-regulation-of-cell-signalling",{"openalex":3908,"mag":3910,"title":3912,"pm":3914,"doi":3916},{"VOID":3909},"W1968323673",{"VOID":3911},"1968323673",{"EN":3913},"Clathrin- and non-clathrin-mediated endocytic regulation of cell signalling",{"VOID":3915},"15687999",{"VOID":3653},"2025-02-09T14:29:14.757+00:00",[135],"https:\u002F\u002Fwww.nature.com\u002Farticles\u002Fnrm1571",[3921,3940],{"id":3922,"sortIndex":25,"researcher":24,"roles":3923,"affiliations":3924,"properties":3933,"displayName":3937,"givenName":24,"familyName":24},"89c8d8be-69a7-4cd3-bd2b-8ac39da5cc47",[],[3925],{"id":3926,"sortIndex":25,"affiliation":3927,"properties":24},"53520199-97eb-473e-80ee-492a5d5ebfe0",{"id":3926,"createTime":24,"updateTime":24,"relativeEntities":3928,"slug":24,"properties":3929,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":3932,"statistic":24},[],{"title":3930},{"EN":3931},"Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Room 1075, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.",[],{"orcid":3934,"title":3936,"openalex":3938},{"VOID":3935},"https:\u002F\u002Forcid.org\u002F0000-0003-3538-6487",{"EN":3937},"Christine Le Roy",{"VOID":3939},"A5068579932",{"id":3941,"sortIndex":99,"researcher":24,"roles":3942,"affiliations":3943,"properties":3952,"displayName":3956,"givenName":24,"familyName":24},"a078c939-146d-41f0-b56b-63b3986f7a15",[],[3944],{"id":3945,"sortIndex":25,"affiliation":3946,"properties":24},"2d38c7e6-7b73-482f-b156-276302b9995d",{"id":3945,"createTime":24,"updateTime":24,"relativeEntities":3947,"slug":24,"properties":3948,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":3951,"statistic":24},[],{"title":3949},{"EN":3950},"Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Room 1075, Mount Sinai Hospital, Toronto, Canada",[],{"orcid":3953,"title":3955,"openalex":3957},{"VOID":3954},"https:\u002F\u002Forcid.org\u002F0000-0003-0932-0644",{"EN":3956},"Jeffrey L. Wrana",{"VOID":3958},"A5056802106",{"url":24,"publisher":3960,"properties":4007},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":3961,"slug":10,"properties":3962,"entityType":22,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":25,"subjectFields":3967,"manageAffiliations":3976,"indexDatabases":3987,"url":90,"thumbnailPath":24,"statistic":4002,"gsStatistic":24,"type":24,"analyzePriority":24},[],{"country":3963,"eissn":3964,"issn":3965,"title":3966},{"VOID":13},{"VOID":15},{"VOID":17},{"EN":19},[3968,3972],{"id":28,"createTime":24,"updateTime":24,"relativeEntities":3969,"label":3970,"description":3971,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":31},{},{"id":34,"createTime":24,"updateTime":24,"relativeEntities":3973,"label":3974,"description":3975,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":37},{},[3977,3982],{"id":41,"createTime":24,"updateTime":24,"relativeEntities":3978,"slug":24,"properties":3979,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":3981,"statistic":24},[],{"title":3980},{"EN":45},[],{"id":48,"createTime":24,"updateTime":24,"relativeEntities":3983,"slug":24,"properties":3984,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":3986,"statistic":24},[],{"title":3985},{"EN":52},[],[3988,3995],{"id":56,"indexDatabase":3989,"url":69,"indexYears":24,"academicFieldIds":3994,"indexDatabaseRanking":24},{"id":58,"createTime":24,"updateTime":24,"relativeEntities":3990,"label":3991,"description":3992,"key":65,"publicationTags":3993,"standard":24},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":3996,"url":84,"indexYears":85,"academicFieldIds":4001,"indexDatabaseRanking":89},{"id":75,"createTime":24,"updateTime":24,"relativeEntities":3997,"label":3998,"description":3999,"key":81,"publicationTags":4000,"standard":24},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88],{"impactFactor":25,"impactFactorByYear":4003,"i10Index":97,"i10IndexLast5Year":25,"totalPublication":97,"totalPublicationByYear":4004,"totalCitation":100,"totalCitationByYear":4005,"totalCitationPerPublication":106,"totalCitationPerPublicationByYear":4006,"hindexLast5Year":97,"hindex":97},{"2016":93,"2017":94,"2019":95,"2020":96},{"2007":99,"2009":99,"2015":99,"2018":99},{"2007":102,"2009":103,"2015":104,"2018":105},{"2007":102,"2009":103,"2015":104,"2018":105},{"issue":4008,"pages":4010,"volume":4012},{"VOID":4009},"2",{"VOID":4011},"112-126",{"VOID":528},854,{"total":4013,"publishYear":531,"statisticByYear":4015},{"2012":1114,"2013":3332,"2014":1114,"2015":4016,"2016":4017,"2017":4018,"2018":4019,"2019":4020,"2020":4019,"2021":4018,"2022":536,"2023":538,"2024":244,"2025":1016},50,48,36,28,26,"2005-02-01",[67,89],[4024,4028,4032,4036,4040,4044,4048,4052,4056,4060,4064,4068,4072,4076,4080,4084,4088,4092,4096,4100,4104,4108,4112,4116,4120,4124,4128,4132,4136,4140,4144,4148,4152,4156,4160,4164,4168,4172,4176,4180,4184,4188,4192,4196,4198,4202,4206,4210,4214,4218,4222,4226,4230,4234,4238,4242,4246,4250,4254,4258,4262,4266,4270,4274,4278,4282,4286,4290,4294,4298,4302,4306,4310,4314,4318,4322,4326,4330,4334,4338,4342,4345,4349,4353,4357,4361,4365,4369,4372,4375,4379,4383,4387,4391,4394,4398,4402,4406,4410,4414,4418,4422,4426,4430,4434,4438,4440,4444,4448,4452,4456,4460,4464,4468,4472,4476,4480,4484,4488,4492,4496,4500,4504,4508,4512,4516,4520,4524,4528,4532,4536,4540,4544,4548,4552,4556,4560,4564,4568,4572,4576,4580],{"id":24,"text":4025,"url":24,"identifiers":4026},"Lemmon, M. A. Phosphoinositide recognition domains. Traffic 4, 201–213 (2003).",{"doi":4027},"10.1034\u002Fj.1600-0854.2004.00071.x",{"id":24,"text":4029,"url":24,"identifiers":4030},"Simonsen, A., Wurmser, A. E., Emr, S. D. & Stenmark, H. The role of phosphoinositides in membrane transport. Curr. Opin. Cell Biol. 13, 485–492 (2001).",{"doi":4031},"10.1016\u002FS0955-0674(00)00240-4",{"id":24,"text":4033,"url":24,"identifiers":4034},"Comer, F. I. & Parent, C. A. PI 3-kinases and PTEN: how opposites chemoattract. Cell 109, 541–544 (2002).",{"doi":4035},"10.1016\u002FS0092-8674(02)00765-1",{"id":24,"text":4037,"url":24,"identifiers":4038},"Simons, K. & Toomre, D. Lipid rafts and signal transduction. Nature Rev. Mol. Cell Biol. 1, 31–39 (2000). This review and references 5, 9 and 129 (also reviews) present various models for the formation of lipid rafts.",{"doi":4039},"10.1038\u002F35036052",{"id":24,"text":4041,"url":24,"identifiers":4042},"Mayor, S. & Riezman, H. Sorting GPI-anchored proteins. Nature Rev. Mol. Cell Biol. 5, 110–120 (2004).",{"doi":4043},"10.1038\u002Fnrm1309",{"id":24,"text":4045,"url":24,"identifiers":4046},"Jacob, R. et al. Annexin II is required for apical transport in polarized epithelial cells. J. Biol. Chem. 279, 3680–3684 (2004).",{"doi":4047},"10.1074\u002Fjbc.C300503200",{"id":24,"text":4049,"url":24,"identifiers":4050},"Hancock, J. F. Ras proteins: different signals from different locations. Nature Rev. Mol. Cell Biol. 4, 373–384 (2003).",{"doi":4051},"10.1038\u002Fnrm1105",{"id":24,"text":4053,"url":24,"identifiers":4054},"Parton, R. G. & Hancock, J. F. Lipid rafts and plasma membrane microorganization: insights from Ras. Trends Cell Biol. 14, 141–147 (2004).",{"doi":4055},"10.1016\u002Fj.tcb.2004.02.001",{"id":24,"text":4057,"url":24,"identifiers":4058},"Kusumi, A., Koyama-Honda, I. & Suzuki, K. Molecular dynamics and interactions for creation of stimulation-induced stabilized rafts from small unstable steady-state rafts. Traffic 5, 213–230 (2004).",{"doi":4059},"10.1111\u002Fj.1600-0854.2004.0178.x",{"id":24,"text":4061,"url":24,"identifiers":4062},"Drevot, P. et al. TCR signal initiation machinery is pre-assembled and activated in a subset of membrane rafts. EMBO J. 21, 1899–1908 (2002).",{"doi":4063},"10.1093\u002Femboj\u002F21.8.1899",{"id":24,"text":4065,"url":24,"identifiers":4066},"Pierce, S. K. Lipid rafts and B-cell activation. Nature Rev. Immunol. 2, 96–105 (2002).",{"doi":4067},"10.1038\u002Fnri726",{"id":24,"text":4069,"url":24,"identifiers":4070},"Saltiel, A. R. & Pessin, J. E. Insulin signaling in microdomains of the plasma membrane. Traffic 4, 711–716 (2003).",{"doi":4071},"10.1034\u002Fj.1600-0854.2003.00119.x",{"id":24,"text":4073,"url":24,"identifiers":4074},"Tansey, M. G., Baloh, R. H., Milbrandt, J. & Johnson, E. M. Jr. GFRα-mediated localization of RET to lipid rafts is required for effective downstream signaling, differentiation, and neuronal survival. Neuron 25, 611–623 (2000).",{"doi":4075},"10.1016\u002FS0896-6273(00)81064-8",{"id":24,"text":4077,"url":24,"identifiers":4078},"Paratcha, G., Ledda, F. & Ibanez, C. F. The neural cell adhesion molecule NCAM is an alternative signaling receptor for GDNF family ligands. Cell 113, 867–879 (2003).",{"doi":4079},"10.1016\u002FS0092-8674(03)00435-5",{"id":24,"text":4081,"url":24,"identifiers":4082},"Legler, D. F., Micheau, O., Doucey, M. A., Tschopp, J. & Bron, C. Recruitment of TNF receptor 1 to lipid rafts is essential for TNFα-mediated NF-κB activation. Immunity 18, 655–664 (2003).",{"doi":4083},"10.1016\u002FS1074-7613(03)00092-X",{"id":24,"text":4085,"url":24,"identifiers":4086},"Wang, D. et al. CD3\u002FCD28 costimulation-induced NF-κB activation is mediated by recruitment of protein kinase C-θ, Bcl10, and IκB kinase β to the immunological synapse through CARMA1. Mol. Cell. Biol. 24, 164–171 (2004).",{"doi":4087},"10.1128\u002FMCB.24.1.164-171.2003",{"id":24,"text":4089,"url":24,"identifiers":4090},"Sehgal, P. B., Guo, G. G., Shah, M., Kumar, V. & Patel, K. Cytokine signaling: STATS in plasma membrane rafts. J. Biol. Chem. 277, 12067–12074 (2002).",{"doi":4091},"10.1074\u002Fjbc.M200018200",{"id":24,"text":4093,"url":24,"identifiers":4094},"Marmor, M. D. & Yarden, Y. Role of protein ubiquitylation in regulating endocytosis of receptor tyrosine kinases. Oncogene 23, 2057–2070 (2004).",{"doi":4095},"10.1038\u002Fsj.onc.1207390",{"id":24,"text":4097,"url":24,"identifiers":4098},"Nesterov, A., Carter, R. E., Sorkina, T., Gill, G. N. & Sorkin, A. Inhibition of the receptor-binding function of clathrin adaptor protein AP-2 by dominant-negative mutant μ2 subunit and its effects on endocytosis. EMBO J. 18, 2489–2499 (1999).",{"doi":4099},"10.1093\u002Femboj\u002F18.9.2489",{"id":24,"text":4101,"url":24,"identifiers":4102},"Polo, S. et al. A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins. Nature 416, 451–455 (2002). Shows that UIM-containing proteins, which bind ubiquitin, recruit ubiquitin ligases and are themselves monoubiquitylated.",{"doi":4103},"10.1038\u002F416451a",{"id":24,"text":4105,"url":24,"identifiers":4106},"Hicke, L. & Riezman, H. Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cell 84, 277–287 (1996).",{"doi":4107},"10.1016\u002FS0092-8674(00)80982-4",{"id":24,"text":4109,"url":24,"identifiers":4110},"Haglund, K. et al. Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation. Nature Cell Biol. 5, 461–466 (2003).",{"doi":4111},"10.1038\u002Fncb983",{"id":24,"text":4113,"url":24,"identifiers":4114},"Legendre-Guillemin, V., Wasiak, S., Hussain, N. K., Angers, A. & McPherson, P. S. ENTH\u002FANTH proteins and clathrin-mediated membrane budding. J. Cell Sci. 117, 9–18 (2004).",{"doi":4115},"10.1242\u002Fjcs.00928",{"id":24,"text":4117,"url":24,"identifiers":4118},"French, A. R., Tadaki, D. K., Niyogi, S. K. & Lauffenburger, D. A. Intracellular trafficking of epidermal growth factor family ligands is directly influenced by the pH sensitivity of the receptor\u002Fligand interaction. J. Biol. Chem. 270, 4334–4340 (1995).",{"doi":4119},"10.1074\u002Fjbc.270.9.4334",{"id":24,"text":4121,"url":24,"identifiers":4122},"Bao, J. et al. Threonine phosphorylation diverts internalized epidermal growth factor receptors from a degradative pathway to the recycling endosome. J. Biol. Chem. 275, 26178–26186 (2000).",{"doi":4123},"10.1074\u002Fjbc.M002367200",{"id":24,"text":4125,"url":24,"identifiers":4126},"Katzmann, D. J., Babst, M. & Emr, S. D. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 106, 145–155 (2001).",{"doi":4127},"10.1016\u002FS0092-8674(01)00434-2",{"id":24,"text":4129,"url":24,"identifiers":4130},"Bache, K. G., Raiborg, C., Mehlum, A. & Stenmark, H. STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes. J. Biol. Chem. 278, 12513–12521 (2003).",{"doi":4131},"10.1074\u002Fjbc.M210843200",{"id":24,"text":4133,"url":24,"identifiers":4134},"Raiborg, C., Bache, K. G., Mehlum, A., Stang, E. & Stenmark, H. Hrs recruits clathrin to early endosomes. EMBO J. 20, 5008–5021 (2001).",{"doi":4135},"10.1093\u002Femboj\u002F20.17.5008",{"id":24,"text":4137,"url":24,"identifiers":4138},"Katzmann, D. J., Stefan, C. J., Babst, M. & Emr, S. D. Vps27 recruits ESCRT machinery to endosomes during MVB sorting. J. Cell Biol. 162, 413–423 (2003).",{"doi":4139},"10.1083\u002Fjcb.200302136",{"id":24,"text":4141,"url":24,"identifiers":4142},"Bache, K. G., Brech, A., Mehlum, A. & Stenmark, H. Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes. J. Cell Biol. 162, 435–442 (2003).",{"doi":4143},"10.1083\u002Fjcb.200302131",{"id":24,"text":4145,"url":24,"identifiers":4146},"Gruenberg, J. & Stenmark, H. The biogenesis of multivesicular endosomes. Nature Rev. Mol. Cell Biol. 5, 317–323 (2004).",{"doi":4147},"10.1038\u002Fnrm1360",{"id":24,"text":4149,"url":24,"identifiers":4150},"Parton, R. G. & Richards, A. A. Lipid rafts and caveolae as portals for endocytosis: new insights and common mechanisms. Traffic 4, 724–738 (2003).",{"doi":4151},"10.1034\u002Fj.1600-0854.2003.00128.x",{"id":24,"text":4153,"url":24,"identifiers":4154},"Nichols, B. J. GM1-containing lipid rafts are depleted within clathrin-coated pits. Curr. Biol. 13, 686–690 (2003).",{"doi":4155},"10.1016\u002FS0960-9822(03)00209-4",{"id":24,"text":4157,"url":24,"identifiers":4158},"Nichols, B. Caveosomes and endocytosis of lipid rafts. J. Cell Sci. 116, 4707–4714 (2003).",{"doi":4159},"10.1242\u002Fjcs.00840",{"id":24,"text":4161,"url":24,"identifiers":4162},"Sato, S. B. et al. Distribution and transport of cholesterol-rich membrane domains monitored by a membrane-impermeant fluorescent polyethylene glycol-derivatized cholesterol. J. Biol. Chem. 279, 23790–23796 (2004).",{"doi":4163},"10.1074\u002Fjbc.M313568200",{"id":24,"text":4165,"url":24,"identifiers":4166},"Sharma, D. K. et al. Selective stimulation of caveolar endocytosis by glycosphingolipids and cholesterol. Mol. Biol. Cell 15, 3114–3122 (2004).",{"doi":4167},"10.1091\u002Fmbc.e04-03-0189",{"id":24,"text":4169,"url":24,"identifiers":4170},"Nabi, I. R. & Le, P. U. Caveolae\u002Fraft-dependent endocytosis. J. Cell Biol. 161, 673–677 (2003).",{"doi":4171},"10.1083\u002Fjcb.200302028",{"id":24,"text":4173,"url":24,"identifiers":4174},"Parton, R. G., Joggerst, B. & Simons, K. Regulated internalization of caveolae. J. Cell Biol. 127, 1199–1215 (1994).",{"doi":4175},"10.1083\u002Fjcb.127.5.1199",{"id":24,"text":4177,"url":24,"identifiers":4178},"Pelkmans, L., Puntener, D. & Helenius, A. Local actin polymerization and dynamin recruitment in SV40-induced internalization of caveolae. Science 296, 535–539 (2002).",{"doi":4179},"10.1126\u002Fscience.1069784",{"id":24,"text":4181,"url":24,"identifiers":4182},"Mundy, D. I., Machleidt, T., Ying, Y. S., Anderson, R. G. & Bloom, G. S. Dual control of caveolar membrane traffic by microtubules and the actin cytoskeleton. J. Cell Sci. 115, 4327–4339 (2002).",{"doi":4183},"10.1242\u002Fjcs.00117",{"id":24,"text":4185,"url":24,"identifiers":4186},"Pelkmans, L., Burli, T., Zerial, M. & Helenius, A. Caveolin-stabilized membrane domains as multifunctional transport and sorting devices in endocytic membrane traffic. Cell 118, 767–780 (2004).",{"doi":4187},"10.1016\u002Fj.cell.2004.09.003",{"id":24,"text":4189,"url":24,"identifiers":4190},"Le, P. U. & Nabi, I. R. Distinct caveolae-mediated endocytic pathways target the Golgi apparatus and the endoplasmic reticulum. J. Cell Sci. 116, 1059–1071 (2003).",{"doi":4191},"10.1242\u002Fjcs.00327",{"id":24,"text":4193,"url":24,"identifiers":4194},"Lu, Z., Ghosh, S., Wang, Z. & Hunter, T. Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of β-catenin, and enhanced tumor cell invasion. Cancer Cell 4, 499–515 (2003).",{"doi":4195},"10.1016\u002FS1535-6108(03)00304-0",{"id":24,"text":700,"url":24,"identifiers":4197},{"doi":702},{"id":24,"text":4199,"url":24,"identifiers":4200},"Lamaze, C. et al. Interleukin 2 receptors and detergent-resistant membrane domains define a clathrin-independent endocytic pathway. Mol. Cell 7, 661–671 (2001).",{"doi":4201},"10.1016\u002FS1097-2765(01)00212-X",{"id":24,"text":4203,"url":24,"identifiers":4204},"Sabharanjak, S., Sharma, P., Parton, R. G. & Mayor, S. GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway. Dev. Cell 2, 411–423 (2002). Shows that GPI-anchored proteins can be internalized through a caveolae-negative, lipid-raft pathway, can reach tubular–vesicular endosomes and can traffic back to the plasma membrane through the recycling endosome compartment. Provides the first direct evidence for crosstalk between the lipid-raft internalization pathway and the classic endosomal system.",{"doi":4205},"10.1016\u002FS1534-5807(02)00145-4",{"id":24,"text":4207,"url":24,"identifiers":4208},"Kirchhausen, T. Clathrin adaptors really adapt. Cell 109, 413–416 (2002).",{"doi":4209},"10.1016\u002FS0092-8674(02)00751-1",{"id":24,"text":4211,"url":24,"identifiers":4212},"Schlessinger, J. Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell 110, 669–672 (2002).",{"doi":4213},"10.1016\u002FS0092-8674(02)00966-2",{"id":24,"text":4215,"url":24,"identifiers":4216},"Mineo, C., Gill, G. N. & Anderson, R. G. Regulated migration of epidermal growth factor receptor from caveolae. J. Biol. Chem. 274, 30636–30643 (1999).",{"doi":4217},"10.1074\u002Fjbc.274.43.30636",{"id":24,"text":4219,"url":24,"identifiers":4220},"Roepstorff, K., Thomsen, P., Sandvig, K. & van Deurs, B. Sequestration of epidermal growth factor receptors in non-caveolar lipid rafts inhibits ligand binding. J. Biol. Chem. 277, 18954–18960 (2002).",{"doi":4221},"10.1074\u002Fjbc.M201422200",{"id":24,"text":4223,"url":24,"identifiers":4224},"Pike, L. J. & Casey, L. Localization and turnover of phosphatidylinositol 4,5-bisphosphate in caveolin-enriched membrane domains. J. Biol. Chem. 271, 26453–26456 (1996).",{"doi":4225},"10.1074\u002Fjbc.271.43.26453",{"id":24,"text":4227,"url":24,"identifiers":4228},"Yamabhai, M. & Anderson, R. G. Second cysteine-rich region of epidermal growth factor receptor contains targeting information for caveolae\u002Frafts. J. Biol. Chem. 277, 24843–24846 (2002).",{"doi":4229},"10.1074\u002Fjbc.C200277200",{"id":24,"text":4231,"url":24,"identifiers":4232},"Anderson, R. G. The caveolae membrane system. Annu. Rev. Biochem. 67, 199–225 (1998).",{"doi":4233},"10.1146\u002Fannurev.biochem.67.1.199",{"id":24,"text":4235,"url":24,"identifiers":4236},"de Melker, A. A., van der Horst, G., Calafat, J., Jansen, H. & Borst, J. c-Cbl ubiquitinates the EGF receptor at the plasma membrane and remains receptor associated throughout the endocytic route. J. Cell Sci. 114, 2167–2178 (2001).",{"doi":4237},"10.1242\u002Fjcs.114.11.2167",{"id":24,"text":4239,"url":24,"identifiers":4240},"Peter, B. J. et al. BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science 303, 495–499 (2004).",{"doi":4241},"10.1126\u002Fscience.1092586",{"id":24,"text":4243,"url":24,"identifiers":4244},"Soubeyran, P., Kowanetz, K., Szymkiewicz, I., Langdon, W. Y. & Dikic, I. Cbl–CIN85–endophilin complex mediates ligand-induced downregulation of EGF receptors. Nature 416, 183–187 (2002).",{"doi":4245},"10.1038\u002F416183a",{"id":24,"text":4247,"url":24,"identifiers":4248},"Wilde, A. et al. EGF receptor signaling stimulates SRC kinase phosphorylation of clathrin, influencing clathrin redistribution and EGF uptake. Cell 96, 677–687 (1999).",{"doi":4249},"10.1016\u002FS0092-8674(00)80578-4",{"id":24,"text":4251,"url":24,"identifiers":4252},"Confalonieri, S., Salcini, A. E., Puri, C., Tacchetti, C. & Di Fiore, P. P. Tyrosine phosphorylation of Eps15 is required for ligand-regulated, but not constitutive, endocytosis. J. Cell Biol. 150, 905–912 (2000).",{"doi":4253},"10.1083\u002Fjcb.150.4.905",{"id":24,"text":4255,"url":24,"identifiers":4256},"Salcini, A. E., Chen, H., Iannolo, G., De Camilli, P. & Di Fiore, P. P. Epidermal growth factor pathway substrate 15, Eps15. Int. J. Biochem. Cell Biol. 31, 805–809 (1999).",{"doi":4257},"10.1016\u002FS1357-2725(99)00042-4",{"id":24,"text":4259,"url":24,"identifiers":4260},"Katzmann, D. J., Odorizzi, G. & Emr, S. D. Receptor downregulation and multivesicular-body sorting. Nature Rev. Mol. Cell Biol. 3, 893–905 (2002).",{"doi":4261},"10.1038\u002Fnrm973",{"id":24,"text":4263,"url":24,"identifiers":4264},"Bache, K. G., Raiborg, C., Mehlum, A., Madshus, I. H. & Stenmark, H. Phosphorylation of Hrs downstream of the epidermal growth factor receptor. Eur. J. Biochem. 269, 3881–3887 (2002).",{"doi":4265},"10.1046\u002Fj.1432-1033.2002.03046.x",{"id":24,"text":4267,"url":24,"identifiers":4268},"McPherson, P. S., Kay, B. K. & Hussain, N. K. Signaling on the endocytic pathway. Traffic 2, 375–384 (2001).",{"doi":4269},"10.1034\u002Fj.1600-0854.2001.002006375.x",{"id":24,"text":4271,"url":24,"identifiers":4272},"Yarden, Y. & Sliwkowski, M. X. Untangling the ErbB signalling network. Nature Rev. Mol. Cell Biol. 2, 127–137 (2001).",{"doi":4273},"10.1038\u002F35052073",{"id":24,"text":4275,"url":24,"identifiers":4276},"Wells, A. et al. Ligand-induced transformation by a noninternalizing epidermal growth factor receptor. Science 247, 962–964 (1990).",{"doi":4277},"10.1126\u002Fscience.2305263",{"id":24,"text":4279,"url":24,"identifiers":4280},"Di Fiore, P. P. & Gill, G. N. Endocytosis and mitogenic signaling. Curr. Opin. Cell Biol. 11, 483–488 (1999).",{"doi":4281},"10.1016\u002FS0955-0674(99)80069-6",{"id":24,"text":4283,"url":24,"identifiers":4284},"Vieira, A. V., Lamaze, C. & Schmid, S. L. Control of EGF receptor signaling by clathrin-mediated endocytosis. Science 274, 2086–2089 (1996).",{"doi":4285},"10.1126\u002Fscience.274.5295.2086",{"id":24,"text":4287,"url":24,"identifiers":4288},"Di Guglielmo, G. M., Baass, P. C., Ou, W. J., Posner, B. I. & Bergeron, J. J. Compartmentalization of SHC, GRB2 and mSOS, and hyperphosphorylation of Raf-1 by EGF but not insulin in liver parenchyma. EMBO J. 13, 4269–4277 (1994). Together, references 66 and 67 were the first to show that signalling occurs during EGFR endocytosis.",{"doi":4289},"10.1002\u002Fj.1460-2075.1994.tb06747.x",{"id":24,"text":4291,"url":24,"identifiers":4292},"Haugh, J. M., Huang, A. C., Wiley, H. S., Wells, A. & Lauffenburger, D. A. Internalized epidermal growth factor receptors participate in the activation of p21(ras) in fibroblasts. J. Biol. Chem. 274, 34350–34360 (1999).",{"doi":4293},"10.1074\u002Fjbc.274.48.34350",{"id":24,"text":4295,"url":24,"identifiers":4296},"Kranenburg, O., Verlaan, I. & Moolenaar, W. H. Dynamin is required for the activation of mitogen-activated protein (MAP) kinase by MAP kinase kinase. J. Biol. Chem. 274, 35301–35304 (1999).",{"doi":4297},"10.1074\u002Fjbc.274.50.35301",{"id":24,"text":4299,"url":24,"identifiers":4300},"Wang, Y., Pennock, S., Chen, X. & Wang, Z. Endosomal signaling of epidermal growth factor receptor stimulates signal transduction pathways leading to cell survival. Mol. Cell. Biol. 22, 7279–7290 (2002).",{"doi":4301},"10.1128\u002FMCB.22.20.7279-7290.2002",{"id":24,"text":4303,"url":24,"identifiers":4304},"Howe, C. L., Valletta, J. S., Rusnak, A. S. & Mobley, W. C. NGF signaling from clathrin-coated vesicles: evidence that signaling endosomes serve as a platform for the Ras–MAPK pathway. Neuron 32, 801–814 (2001).",{"doi":4305},"10.1016\u002FS0896-6273(01)00526-8",{"id":24,"text":4307,"url":24,"identifiers":4308},"Teis, D., Wunderlich, W. & Huber, L. A. Localization of the MP1–MAPK scaffold complex to endosomes is mediated by p14 and required for signal transduction. Dev. Cell 3, 803–814 (2002).",{"doi":4309},"10.1016\u002FS1534-5807(02)00364-7",{"id":24,"text":4311,"url":24,"identifiers":4312},"Ohba, Y., Kurokawa, K. & Matsuda, M. Mechanism of the spatio-temporal regulation of Ras and Rap1. EMBO J. 22, 859–869 (2003).",{"doi":4313},"10.1093\u002Femboj\u002Fcdg087",{"id":24,"text":4315,"url":24,"identifiers":4316},"Roy, S., Wyse, B. & Hancock, J. F. H-Ras signaling and K-Ras signaling are differentially dependent on endocytosis. Mol. Cell. Biol. 22, 5128–5140 (2002).",{"doi":4317},"10.1128\u002FMCB.22.14.5128-5140.2002",{"id":24,"text":4319,"url":24,"identifiers":4320},"Carpenter, G. The EGF receptor: a nexus for trafficking and signaling. Bioessays 22, 697–707 (2000).",{"doi":4321},"10.1002\u002F1521-1878(200008)22:8\u003C697::AID-BIES3>3.0.CO;2-1",{"id":24,"text":4323,"url":24,"identifiers":4324},"Mineo, C., James, G. L., Smart, E. J. & Anderson, R. G. Localization of epidermal growth factor-stimulated Ras\u002FRaf-1 interaction to caveolae membrane. J. Biol. Chem. 271, 11930–11935 (1996).",{"doi":4325},"10.1074\u002Fjbc.271.20.11930",{"id":24,"text":4327,"url":24,"identifiers":4328},"Furuchi, T. & Anderson, R. G. Cholesterol depletion of caveolae causes hyperactivation of extracellular signal-related kinase (ERK). J. Biol. Chem. 273, 21099–21104 (1998).",{"doi":4329},"10.1074\u002Fjbc.273.33.21099",{"id":24,"text":4331,"url":24,"identifiers":4332},"Vaudry, D., Stork, P. J., Lazarovici, P. & Eiden, L. E. Signaling pathways for PC12 cell differentiation: making the right connections. Science 296, 1648–1649 (2002).",{"doi":4333},"10.1126\u002Fscience.1071552",{"id":24,"text":4335,"url":24,"identifiers":4336},"Pennock, S. & Wang, Z. Stimulation of cell proliferation by endosomal epidermal growth factor receptor as revealed through two distinct phases of signaling. Mol. Cell. Biol. 23, 5803–5815 (2003).",{"doi":4337},"10.1128\u002FMCB.23.16.5803-5815.2003",{"id":24,"text":4339,"url":24,"identifiers":4340},"Levkowitz, G. et al. c-Cbl\u002FSli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor. Genes Dev. 12, 3663–3674 (1998).",{"doi":4341},"10.1101\u002Fgad.12.23.3663",{"id":24,"text":4343,"url":24,"identifiers":4344},"Klapper, L. N., Waterman, H., Sela, M. & Yarden, Y. Tumor-inhibitory antibodies to HER-2\u002FErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of HER-2. Cancer Res. 60, 3384–3388 (2000).",{},{"id":24,"text":4346,"url":24,"identifiers":4347},"Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783–792 (2001).",{"doi":4348},"10.1056\u002FNEJM200103153441101",{"id":24,"text":4350,"url":24,"identifiers":4351},"Mohney, R. P. et al. Intersectin activates Ras but stimulates transcription through an independent pathway involving JNK. J. Biol. Chem. 278, 47038–47045 (2003).",{"doi":4352},"10.1074\u002Fjbc.M303895200",{"id":24,"text":4354,"url":24,"identifiers":4355},"Miaczynska, M. et al. APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. Cell 116, 445–456 (2004).",{"doi":4356},"10.1016\u002FS0092-8674(04)00117-5",{"id":24,"text":4358,"url":24,"identifiers":4359},"Derynck, R. & Zhang, Y. E. Smad-dependent and Smad-independent pathways in TGF-β family signalling. Nature 425, 577–584 (2003).",{"doi":4360},"10.1038\u002Fnature02006",{"id":24,"text":4362,"url":24,"identifiers":4363},"Wrana, J. L., Attisano, L., Wieser, R., Ventura, F. & Massague, J. Mechanism of activation of the TGF-β receptor. Nature 370, 341–347 (1994).",{"doi":4364},"10.1038\u002F370341a0",{"id":24,"text":4366,"url":24,"identifiers":4367},"Tsukazaki, T., Chiang, T. A., Davison, A. F., Attisano, L. & Wrana, J. L. SARA, a FYVE domain protein that recruits Smad2 to the TGFβ receptor. Cell 95, 779–791 (1998).",{"doi":4368},"10.1016\u002FS0092-8674(00)81701-8",{"id":24,"text":4370,"url":24,"identifiers":4371},"Kavsak, P. et al. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGFβ receptor for degradation. Mol. Cell 6, 1365–1375 (2000).",{"doi":3433},{"id":24,"text":4373,"url":24,"identifiers":4374},"Ebisawa, T. et al. Smurf1 interacts with transforming growth factor-β type I receptor through Smad7 and induces receptor degradation. J. Biol. Chem. 276, 12477–12480 (2001).",{"doi":3437},{"id":24,"text":4376,"url":24,"identifiers":4377},"Zwaagstra, J. C., Kassam, Z. & O'Connor-McCourt, M. D. Down-regulation of transforming growth factor-β receptors: cooperativity between the types I, II, and III receptors and modulation at the cell surface. Exp. Cell Res. 252, 352–362 (1999).",{"doi":4378},"10.1006\u002Fexcr.1999.4640",{"id":24,"text":4380,"url":24,"identifiers":4381},"Garamszegi, N. et al. Transforming growth factor β receptor signaling and endocytosis are linked through a COOH terminal activation motif in the type I receptor. Mol. Biol. Cell 12, 2881–2893 (2001).",{"doi":4382},"10.1091\u002Fmbc.12.9.2881",{"id":24,"text":4384,"url":24,"identifiers":4385},"Anders, R. A., Dore, J. J. Jr, Arline, S. L., Garamszegi, N. & Leof, E. B. Differential requirement for type I and type II transforming growth factor β receptor kinase activity in ligand-mediated receptor endocytosis. J. Biol. Chem. 273, 23118–23125 (1998).",{"doi":4386},"10.1074\u002Fjbc.273.36.23118",{"id":24,"text":4388,"url":24,"identifiers":4389},"Ehrlich, M., Shmuely, A. & Henis, Y. I. A single internalization signal from the di-leucine family is critical for constitutive endocytosis of the type II TGF-β receptor. J. Cell Sci. 114, 1777–1786 (2001).",{"doi":4390},"10.1242\u002Fjcs.114.9.1777",{"id":24,"text":4392,"url":24,"identifiers":4393},"Di Guglielmo, G. M., Le Roy, C., Goodfellow, A. F. & Wrana, J. L. Distinct endocytic pathways regulate TGF-β receptor signalling and turnover. Nature Cell Biol. 5, 410–421 (2003). Shows that cell-surface TGFβRs are subjected to a dynamic compartmentalization between raft and non-raft membranes, and can traffic through distinct clathrin-dependent and clathrin-independent endocytic routes that regulate signalling and degradation, respectively.",{"doi":3649},{"id":24,"text":4395,"url":24,"identifiers":4396},"Yao, D., Ehrlich, M., Henis, Y. I. & Leof, E. B. Transforming growth factor-β receptors interact with AP2 by direct binding to β2 subunit. Mol. Biol. Cell 13, 4001–4012 (2002).",{"doi":4397},"10.1091\u002Fmbc.02-07-0104",{"id":24,"text":4399,"url":24,"identifiers":4400},"Chen, W. et al. β-arrestin 2 mediates endocytosis of type III TGF-β receptor and down-regulation of its signaling. Science 301, 1394–1397 (2003).",{"doi":4401},"10.1126\u002Fscience.1083195",{"id":24,"text":4403,"url":24,"identifiers":4404},"Hayes, S., Chawla, A. & Corvera, S. TGFβ receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2. J. Cell Biol. 158, 1239–1249 (2002).",{"doi":4405},"10.1083\u002Fjcb.200204088",{"id":24,"text":4407,"url":24,"identifiers":4408},"Mitchell, H., Choudhury, A., Pagano, R. E. & Leof, E. B. Ligand-dependent and-independent TGF-β receptor recycling regulated by clathrin-mediated endocytosis and Rab11. Mol. Biol. Cell 15, 4166–4178 (2004).",{"doi":4409},"10.1091\u002Fmbc.e04-03-0245",{"id":24,"text":4411,"url":24,"identifiers":4412},"Itoh, F. et al. The FYVE domain in Smad anchor for receptor activation (SARA) is sufficient for localization of SARA in early endosomes and regulates TGF-β\u002FSmad signalling. Genes Cells 7, 321–331 (2002).",{"doi":4413},"10.1046\u002Fj.1365-2443.2002.00519.x",{"id":24,"text":4415,"url":24,"identifiers":4416},"Panopoulou, E. et al. Early endosomal regulation of Smad-dependent signaling in endothelial cells. J. Biol. Chem. 277, 18046–18052 (2002).",{"doi":4417},"10.1074\u002Fjbc.M107983200",{"id":24,"text":4419,"url":24,"identifiers":4420},"Lin, H. K., Bergmann, S. & Pandolfi, P. P. Cytoplasmic PML function in TGF-β signalling. Nature 431, 205–211 (2004).",{"doi":4421},"10.1038\u002Fnature02783",{"id":24,"text":4423,"url":24,"identifiers":4424},"Miura, S. et al. Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA. Mol. Cell. Biol. 20, 9346–9355 (2000).",{"doi":4425},"10.1128\u002FMCB.20.24.9346-9355.2000",{"id":24,"text":4427,"url":24,"identifiers":4428},"Razani, B. et al. Caveolin-1 regulates transforming growth factor (TGF)-β\u002FSMAD signaling through an interaction with the TGF-β type I receptor. J. Biol. Chem. 276, 6727–6738 (2001).",{"doi":4429},"10.1074\u002Fjbc.M008340200",{"id":24,"text":4431,"url":24,"identifiers":4432},"Lu, Z. et al. Transforming growth factor β activates Smad2 in the absence of receptor endocytosis. J. Biol. Chem. 277, 29363–29368 (2002).",{"doi":4433},"10.1074\u002Fjbc.M203495200",{"id":24,"text":4435,"url":24,"identifiers":4436},"Razani, B., Woodman, S. E. & Lisanti, M. P. Caveolae: from cell biology to animal physiology. Pharmacol. Rev. 54, 431–467 (2002).",{"doi":4437},"10.1124\u002Fpr.54.3.431",{"id":24,"text":3627,"url":24,"identifiers":4439},{"doi":3629},{"id":24,"text":4441,"url":24,"identifiers":4442},"Hemar, A. et al. Endocytosis of interleukin 2 receptors in human T lymphocytes: distinct intracellular localization and fate of the receptor α, β, and γ chains. J. Cell Biol. 129, 55–64 (1995).",{"doi":4443},"10.1083\u002Fjcb.129.1.55",{"id":24,"text":4445,"url":24,"identifiers":4446},"Benlimame, N., Le, P. U. & Nabi, I. R. Localization of autocrine motility factor receptor to caveolae and clathrin-independent internalization of its ligand to smooth endoplasmic reticulum. Mol. Biol. Cell 9, 1773–1786 (1998).",{"doi":4447},"10.1091\u002Fmbc.9.7.1773",{"id":24,"text":4449,"url":24,"identifiers":4450},"Le, P. U., Guay, G., Altschuler, Y. & Nabi, I. R. Caveolin-1 is a negative regulator of caveolae-mediated endocytosis to the endoplasmic reticulum. J. Biol. Chem. 277, 3371–3379 (2002).",{"doi":4451},"10.1074\u002Fjbc.M111240200",{"id":24,"text":4453,"url":24,"identifiers":4454},"Pelkmans, L., Kartenbeck, J. & Helenius, A. Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nature Cell Biol. 3, 473–483 (2001). This is an elegant study of a viral internalization route through a caveolar\u002Flipid-raft endocytic pathway.",{"doi":4455},"10.1038\u002F35074539",{"id":24,"text":4457,"url":24,"identifiers":4458},"Nichols, B. J. A distinct class of endosome mediates clathrin-independent endocytosis to the Golgi complex. Nature Cell Biol. 4, 374–378 (2002).",{"doi":4459},"10.1038\u002Fncb787",{"id":24,"text":4461,"url":24,"identifiers":4462},"Nichols, B. J. et al. Rapid cycling of lipid raft markers between the cell surface and Golgi complex. J. Cell Biol. 153, 529–541 (2001).",{"doi":4463},"10.1083\u002Fjcb.153.3.529",{"id":24,"text":4465,"url":24,"identifiers":4466},"Denef, N., Neubuser, D., Perez, L. & Cohen, S. M. Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened. Cell 102, 521–531 (2000).",{"doi":4467},"10.1016\u002FS0092-8674(00)00056-8",{"id":24,"text":4469,"url":24,"identifiers":4470},"Incardona, J. P. et al. Receptor-mediated endocytosis of soluble and membrane-tethered Sonic hedgehog by Patched-1. Proc. Natl Acad. Sci. USA 97, 12044–12049 (2000).",{"doi":4471},"10.1073\u002Fpnas.220251997",{"id":24,"text":4473,"url":24,"identifiers":4474},"Zhu, A. J., Zheng, L., Suyama, K. & Scott, M. P. Altered localization of Drosophila Smoothened protein activates Hedgehog signal transduction. Genes Dev. 17, 1240–1252 (2003).",{"doi":4475},"10.1101\u002Fgad.1080803",{"id":24,"text":4477,"url":24,"identifiers":4478},"Incardona, J. P., Gruenberg, J. & Roelink, H. Sonic hedgehog induces the segregation of patched and smoothened in endosomes. Curr. Biol. 12, 983–995 (2002). In this study, the authors propose a model in which the trafficking of Ptc–Shh towards lysosomes regulates Smo signalling activity.",{"doi":4479},"10.1016\u002FS0960-9822(02)00895-3",{"id":24,"text":4481,"url":24,"identifiers":4482},"Karpen, H. E. et al. The sonic hedgehog receptor patched associates with caveolin-1 in cholesterol-rich microdomains of the plasma membrane. J. Biol. Chem. 276, 19503–19511 (2001).",{"doi":4483},"10.1074\u002Fjbc.M010832200",{"id":24,"text":4485,"url":24,"identifiers":4486},"Rietveld, A., Neutz, S., Simons, K. & Eaton, S. Association of sterol- and glycosylphosphatidylinositol-linked proteins with Drosophila raft lipid microdomains. J. Biol. Chem. 274, 12049–12054 (1999).",{"doi":4487},"10.1074\u002Fjbc.274.17.12049",{"id":24,"text":4489,"url":24,"identifiers":4490},"Dubois, L., Lecourtois, M., Alexandre, C., Hirst, E. & Vincent, J. P. Regulated endocytic routing modulates wingless signaling in Drosophila embryos. Cell 105, 613–624 (2001). This study links the distribution of Wg, its signalling and its trafficking. It shows that the range of Wg signalling is controlled by its lysosomal degradation, and is regulated by EGF.",{"doi":4491},"10.1016\u002FS0092-8674(01)00375-0",{"id":24,"text":4493,"url":24,"identifiers":4494},"Chen, W. et al. Dishevelled 2 recruits β-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4. Science 301, 1391–1394 (2003).",{"doi":4495},"10.1126\u002Fscience.1082808",{"id":24,"text":4497,"url":24,"identifiers":4498},"Mao, B. et al. Kremen proteins are Dickkopf receptors that regulate Wnt\u002Fβ-catenin signalling. Nature 417, 664–667 (2002).",{"doi":4499},"10.1038\u002Fnature756",{"id":24,"text":4501,"url":24,"identifiers":4502},"Willert, K. et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423, 448–452 (2003).",{"doi":4503},"10.1038\u002Fnature01611",{"id":24,"text":4505,"url":24,"identifiers":4506},"Zacharias, D. A., Violin, J. D., Newton, A. C. & Tsien, R. Y. Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science 296, 913–916 (2002).",{"doi":4507},"10.1126\u002Fscience.1068539",{"id":24,"text":4509,"url":24,"identifiers":4510},"Hurley, J. H. & Meyer, T. Subcellular targeting by membrane lipids. Curr. Opin. Cell Biol. 13, 146–152 (2001).",{"doi":4511},"10.1016\u002FS0955-0674(00)00191-5",{"id":24,"text":4513,"url":24,"identifiers":4514},"Varma, R. & Mayor, S. GPI-anchored proteins are organized in submicron domains at the cell surface. Nature 394, 798–801 (1998).",{"doi":4515},"10.1038\u002F29563",{"id":24,"text":4517,"url":24,"identifiers":4518},"Friedrichson, T. & Kurzchalia, T. V. Microdomains of GPI-anchored proteins in living cells revealed by crosslinking. Nature 394, 802–805 (1998).",{"doi":4519},"10.1038\u002F29570",{"id":24,"text":4521,"url":24,"identifiers":4522},"Harder, T., Scheiffele, P., Verkade, P. & Simons, K. Lipid domain structure of the plasma membrane revealed by patching of membrane components. J. Cell Biol. 141, 929–942 (1998). Shows that proteins can be segregated between lipid-raft microdomains and non-lipid-raft membranes.",{"doi":4523},"10.1083\u002Fjcb.141.4.929",{"id":24,"text":4525,"url":24,"identifiers":4526},"Schuck, S., Honsho, M., Ekroos, K., Shevchenko, A. & Simons, K. Resistance of cell membranes to different detergents. Proc. Natl Acad. Sci. USA 100, 5795–5800 (2003).",{"doi":4527},"10.1073\u002Fpnas.0631579100",{"id":24,"text":4529,"url":24,"identifiers":4530},"Anderson, R. G. & Jacobson, K. A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296, 1821–1825 (2002).",{"doi":4531},"10.1126\u002Fscience.1068886",{"id":24,"text":4533,"url":24,"identifiers":4534},"Pike, L. J. Lipid rafts: heterogeneity on the high seas. Biochem. J. 378, 281–292 (2004).",{"doi":4535},"10.1042\u002Fbj20031672",{"id":24,"text":4537,"url":24,"identifiers":4538},"McCabe, J. B. & Berthiaume, L. G. N-terminal protein acylation confers localization to cholesterol, sphingolipid-enriched membranes but not to lipid rafts\u002Fcaveolae. Mol. Biol. Cell 12, 3601–3617 (2001).",{"doi":4539},"10.1091\u002Fmbc.12.11.3601",{"id":24,"text":4541,"url":24,"identifiers":4542},"Kimura, A., Baumann, C. A., Chiang, S. H. & Saltiel, A. R. The sorbin homology domain: a motif for the targeting of proteins to lipid rafts. Proc. Natl Acad. Sci. USA 98, 9098–9103 (2001).",{"doi":4543},"10.1073\u002Fpnas.151252898",{"id":24,"text":4545,"url":24,"identifiers":4546},"Plant, P. J. et al. Apical membrane targeting of Nedd4 is mediated by an association of its C2 domain with annexin XIIIb. J. Cell Biol. 149, 1473–1484 (2000).",{"doi":4547},"10.1083\u002Fjcb.149.7.1473",{"id":24,"text":4549,"url":24,"identifiers":4550},"Kirchhausen, T. Clathrin . Annu. Rev. Biochem. 69, 699–727 (2000).",{"doi":4551},"10.1146\u002Fannurev.biochem.69.1.699",{"id":24,"text":4553,"url":24,"identifiers":4554},"Bonifacino, J. S. & Lippincott-Schwartz, J. Coat proteins: shaping membrane transport. Nature Rev. Mol. Cell Biol. 4, 409–414 (2003).",{"doi":4555},"10.1038\u002Fnrm1099",{"id":24,"text":4557,"url":24,"identifiers":4558},"Murphy, R. F. Maturation models for endosome and lysosome biogenesis. Trends Cell Biol. 1, 77–82 (1991).",{"doi":4559},"10.1016\u002F0962-8924(91)90022-2",{"id":24,"text":4561,"url":24,"identifiers":4562},"Griffiths, G. & Gruenberg, J. The arguments for pre-existing early and late endosomes. Trends Cell Biol. 1, 5–9 (1991).",{"doi":4563},"10.1016\u002F0962-8924(91)90047-D",{"id":24,"text":4565,"url":24,"identifiers":4566},"Bishop, N. E. Dynamics of endosomal sorting. Int. Rev. Cytol. 232, 1–57 (2003).",{"doi":4567},"10.1016\u002FS0074-7696(03)32001-7",{"id":24,"text":4569,"url":24,"identifiers":4570},"Rothberg, K. G. et al. Caveolin, a protein component of caveolae membrane coats. Cell 68, 673–682 (1992).",{"doi":4571},"10.1016\u002F0092-8674(92)90143-Z",{"id":24,"text":4573,"url":24,"identifiers":4574},"Drab, M. et al. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science 293, 2449–2452 (2001).",{"doi":4575},"10.1126\u002Fscience.1062688",{"id":24,"text":4577,"url":24,"identifiers":4578},"Fra, A. M., Williamson, E., Simons, K. & Parton, R. G. De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin. Proc. Natl Acad. Sci. USA 92, 8655–8659 (1995).",{"doi":4579},"10.1073\u002Fpnas.92.19.8655",{"id":24,"text":4581,"url":24,"identifiers":4582},"Kurzchalia, T. V. & Parton, R. G. Membrane microdomains and caveolae. Curr. Opin. Cell Biol. 11, 424–431 (1999).",{"doi":4583},"10.1016\u002FS0955-0674(99)80061-1",{"id":4585,"createTime":4586,"updateTime":4586,"relativeEntities":4587,"slug":4588,"properties":4589,"entityType":131,"verifyStatus":132,"verifyTime":4586,"verifyNote":133,"languages":4600,"translateLanguages":24,"viewCount":25,"primaryUrl":4601,"fullTextUrl":24,"authors":4602,"publicationType":174,"publisherRelationship":4637,"citationCount":4690,"citationInfo":4691,"publishDate":4697,"publishYear":531,"citationAnalyzeStatus":23,"lastCitationAnalyze":24,"indexDatabases":4698,"openAccess":24,"references":4699,"isForceReanalyzing":409},"67041695-83f5-45eb-b3cb-3edae6f7ed87","2025-02-09T04:22:34.707+00:00",[],"What-is-the-role-of-protein-aggregation-in-neurodegeneration-",{"openalex":4590,"mag":4592,"title":4594,"pm":4596,"doi":4598},{"VOID":4591},"W1565076702",{"VOID":4593},"1565076702",{"EN":4595},"What is the role of protein aggregation in neurodegeneration?",{"VOID":4597},"16167052",{"VOID":4599},"10.1038\u002Fnrm1742",[135],"https:\u002F\u002Fwww.nature.com\u002Farticles\u002Fnrm1742",[4603,4622],{"id":4604,"sortIndex":25,"researcher":24,"roles":4605,"affiliations":4606,"properties":4615,"displayName":4619,"givenName":24,"familyName":24},"3ede6c57-53b7-4c21-9ef3-d531497f1f54",[],[4607],{"id":4608,"sortIndex":25,"affiliation":4609,"properties":24},"390b4e2c-31df-47a9-8772-685e41bf03a4",{"id":4608,"createTime":24,"updateTime":24,"relativeEntities":4610,"slug":24,"properties":4611,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":4614,"statistic":24},[],{"title":4612},{"EN":4613},"the Division of Neurobiology, Department of Psychiatry at Johns Hopkins University School of Medicine, CMSC 8-121, Baltimore, USA",[],{"orcid":4616,"title":4618,"openalex":4620},{"VOID":4617},"https:\u002F\u002Forcid.org\u002F0000-0003-1882-5847",{"EN":4619},"Christopher A. Ross",{"VOID":4621},"A5072055814",{"id":4623,"sortIndex":99,"researcher":24,"roles":4624,"affiliations":4625,"properties":4632,"displayName":4634,"givenName":24,"familyName":24},"ba09b0a2-dca0-42e7-a426-8079365c514b",[],[4626],{"id":4608,"sortIndex":25,"affiliation":4627,"properties":24},{"id":4608,"createTime":24,"updateTime":24,"relativeEntities":4628,"slug":24,"properties":4629,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":4631,"statistic":24},[],{"title":4630},{"EN":4613},[],{"title":4633,"openalex":4635},{"EN":4634},"Michelle A. Poirier",{"VOID":4636},"A5047331202",{"url":24,"publisher":4638,"properties":4685},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":4639,"slug":10,"properties":4640,"entityType":22,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":25,"subjectFields":4645,"manageAffiliations":4654,"indexDatabases":4665,"url":90,"thumbnailPath":24,"statistic":4680,"gsStatistic":24,"type":24,"analyzePriority":24},[],{"country":4641,"eissn":4642,"issn":4643,"title":4644},{"VOID":13},{"VOID":15},{"VOID":17},{"EN":19},[4646,4650],{"id":28,"createTime":24,"updateTime":24,"relativeEntities":4647,"label":4648,"description":4649,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":31},{},{"id":34,"createTime":24,"updateTime":24,"relativeEntities":4651,"label":4652,"description":4653,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":37},{},[4655,4660],{"id":41,"createTime":24,"updateTime":24,"relativeEntities":4656,"slug":24,"properties":4657,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":4659,"statistic":24},[],{"title":4658},{"EN":45},[],{"id":48,"createTime":24,"updateTime":24,"relativeEntities":4661,"slug":24,"properties":4662,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":4664,"statistic":24},[],{"title":4663},{"EN":52},[],[4666,4673],{"id":56,"indexDatabase":4667,"url":69,"indexYears":24,"academicFieldIds":4672,"indexDatabaseRanking":24},{"id":58,"createTime":24,"updateTime":24,"relativeEntities":4668,"label":4669,"description":4670,"key":65,"publicationTags":4671,"standard":24},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":4674,"url":84,"indexYears":85,"academicFieldIds":4679,"indexDatabaseRanking":89},{"id":75,"createTime":24,"updateTime":24,"relativeEntities":4675,"label":4676,"description":4677,"key":81,"publicationTags":4678,"standard":24},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88],{"impactFactor":25,"impactFactorByYear":4681,"i10Index":97,"i10IndexLast5Year":25,"totalPublication":97,"totalPublicationByYear":4682,"totalCitation":100,"totalCitationByYear":4683,"totalCitationPerPublication":106,"totalCitationPerPublicationByYear":4684,"hindexLast5Year":97,"hindex":97},{"2016":93,"2017":94,"2019":95,"2020":96},{"2007":99,"2009":99,"2015":99,"2018":99},{"2007":102,"2009":103,"2015":104,"2018":105},{"2007":102,"2009":103,"2015":104,"2018":105},{"issue":4686,"pages":4687,"volume":4689},{"VOID":1791},{"VOID":4688},"891-898",{"VOID":528},593,{"total":4690,"publishYear":531,"statisticByYear":4692},{"2012":2148,"2013":4693,"2014":4694,"2015":4695,"2016":4019,"2017":93,"2018":4019,"2019":4696,"2020":238,"2021":536,"2022":234,"2023":1796,"2024":242},38,40,35,29,"2005-11-01",[67,89],[4700,4704,4708,4712,4716,4720,4724,4728,4732,4736,4740,4743,4747,4751,4755,4759,4763,4767,4771,4775,4779,4783,4787,4791,4795,4799,4803,4807,4811,4815,4819,4823,4827,4831,4835,4839,4843,4847,4851,4855,4858,4862,4866,4870,4874,4878,4882,4886,4890,4894,4898,4902,4906,4909,4913,4917,4921,4925,4929,4933,4937,4941,4945,4949,4953,4957,4961,4965,4969,4973,4977,4981,4985,4989,4993,4997,5001,5005,5009,5013,5017,5021,5025,5029,5033,5037,5041,5045,5049],{"id":24,"text":4701,"url":24,"identifiers":4702},"DiFiglia, M. et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990–1993 (1997).",{"doi":4703},"10.1126\u002Fscience.277.5334.1990",{"id":24,"text":4705,"url":24,"identifiers":4706},"Bates, G. Huntingtin aggregation and toxicity in Huntington's disease. Lancet 361, 1642–1644 (2003).",{"doi":4707},"10.1016\u002FS0140-6736(03)13304-1",{"id":24,"text":4709,"url":24,"identifiers":4710},"Selkoe, D. J. Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases. Nature Cell Biol. 6, 1054–1061 (2004).",{"doi":4711},"10.1038\u002Fncb1104-1054",{"id":24,"text":4713,"url":24,"identifiers":4714},"Ross, C. A. & Poirier, M. A. Protein aggregation and neurodegenerative disease. Nature Med. 10, S10–S17 (2004).",{"doi":4715},"10.1038\u002Fnm1066",{"id":24,"text":4717,"url":24,"identifiers":4718},"Cohen, F. E. & Kelly, J. W. Therapeutic approaches to protein-misfolding diseases. Nature 426, 905–909 (2003).",{"doi":4719},"10.1038\u002Fnature02265",{"id":24,"text":4721,"url":24,"identifiers":4722},"Buxbaum, J. N. Diseases of protein conformation: what do in vitro experiments tell us about in vivo diseases? Trends Biochem. Sci. 28, 585–592 (2003).",{"doi":4723},"10.1016\u002Fj.tibs.2003.09.009",{"id":24,"text":4725,"url":24,"identifiers":4726},"Dobson, C. M. Protein folding and misfolding. Nature 426, 884–890 (2003).",{"doi":4727},"10.1038\u002Fnature02261",{"id":24,"text":4729,"url":24,"identifiers":4730},"Stefani, M. & Dobson, C. M. Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution. J. Mol. Med. 81, 678–699 (2003).",{"doi":4731},"10.1007\u002Fs00109-003-0464-5",{"id":24,"text":4733,"url":24,"identifiers":4734},"Dawson, T. M. & Dawson, V. L. Molecular pathways of neurodegeneration in Parkinson's disease. Science 302, 819–822 (2003).",{"doi":4735},"10.1126\u002Fscience.1087753",{"id":24,"text":4737,"url":24,"identifiers":4738},"Bucciantini, M. et al. Prefibrillar amyloid protein aggregates share common features of cytotoxicity. J. Biol. Chem. 279, 31374–31382 (2004).",{"doi":4739},"10.1074\u002Fjbc.M400348200",{"id":24,"text":4741,"url":24,"identifiers":4742},"Makin, O. S. & Serpell, L. C. X-ray diffraction studies of amyloid structure. Methods Mol. Biol. 299, 67–80 (2005).",{},{"id":24,"text":4744,"url":24,"identifiers":4745},"Ross, C. A. & Margolis, R. L. Neurogenetics: insights into degenerative diseases and approaches to schizophrenia. Clin. Neurosci. Res. (in the press).",{"doi":4746},"10.1016\u002Fj.cnr.2005.07.001",{"id":24,"text":4748,"url":24,"identifiers":4749},"Eanes, E. D. & Glenner, G. G. X-ray diffraction studies on amyloid filaments. J. Histochem. Cytochem. 16, 673–677 (1968).",{"doi":4750},"10.1177\u002F16.11.673",{"id":24,"text":4752,"url":24,"identifiers":4753},"Sunde, M. & Blake, C. C. From the globular to the fibrous state: protein structure and structural conversion in amyloid formation. Q. Rev. Biophys. 31, 1–39 (1998).",{"doi":4754},"10.1017\u002FS0033583598003400",{"id":24,"text":4756,"url":24,"identifiers":4757},"Terry, R. D. et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 30, 572–580 (1991).",{"doi":4758},"10.1002\u002Fana.410300410",{"id":24,"text":4760,"url":24,"identifiers":4761},"Tompkins, M. M. & Hill, W. D. Contribution of somal Lewy bodies to neuronal death. Brain Res. 775, 24–29 (1997).",{"doi":4762},"10.1016\u002FS0006-8993(97)00874-3",{"id":24,"text":4764,"url":24,"identifiers":4765},"Gutekunst, C. A. et al. Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J. Neurosci. 19, 2522–2534 (1999).",{"doi":4766},"10.1523\u002FJNEUROSCI.19-07-02522.1999",{"id":24,"text":4768,"url":24,"identifiers":4769},"Kuemmerle, S. et al. Huntington aggregates may not predict neuronal death in Huntington's disease. Ann. Neurol. 46, 842–849 (1999).",{"doi":4770},"10.1002\u002F1531-8249(199912)46:6\u003C842::AID-ANA6>3.0.CO;2-O",{"id":24,"text":4772,"url":24,"identifiers":4773},"Saudou, F., Finkbeiner, S., Devys, D. & Greenberg, M. E. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 95, 55–66 (1998).",{"doi":4774},"10.1016\u002FS0092-8674(00)81782-1",{"id":24,"text":4776,"url":24,"identifiers":4777},"Arrasate, M., Mitra, S., Schweitzer, E. S., Segal, M. R. & Finkbeiner, S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431, 805–810 (2004).",{"doi":4778},"10.1038\u002Fnature02998",{"id":24,"text":4780,"url":24,"identifiers":4781},"Stefanis, L., Larsen, K. E., Rideout, H. J., Sulzer, D. & Greene, L. A. Expression of A53T mutant but not wild-type a-synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death. J. Neurosci. 21, 9549–9560 (2001).",{"doi":4782},"10.1523\u002FJNEUROSCI.21-24-09549.2001",{"id":24,"text":4784,"url":24,"identifiers":4785},"Tanaka, Y. et al. Inducible expression of mutant α-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis. Hum. Mol. Genet. 10, 919–926 (2001).",{"doi":4786},"10.1093\u002Fhmg\u002F10.9.919",{"id":24,"text":4788,"url":24,"identifiers":4789},"Petrucelli, L. et al. Parkin protects against the toxicity associated with mutant α-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons. Neuron 36, 1007–1019 (2002).",{"doi":4790},"10.1016\u002FS0896-6273(02)01125-X",{"id":24,"text":4792,"url":24,"identifiers":4793},"Engelender, S. et al. Synphilin-1 associates with a-synuclein and promotes the formation of cytosolic inclusions. Nature Genet. 22, 110–114 (1999).",{"doi":4794},"10.1038\u002F8820",{"id":24,"text":4796,"url":24,"identifiers":4797},"Tanaka, M. et al. Aggresomes formed by α-synuclein and synphilin-1 are cytoprotective. J. Biol. Chem. 279, 4625–4631 (2004).",{"doi":4798},"10.1074\u002Fjbc.M310994200",{"id":24,"text":4800,"url":24,"identifiers":4801},"Warrick, J. M. et al. Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nature Genet. 23, 425–428 (1999).",{"doi":4802},"10.1038\u002F70532",{"id":24,"text":4804,"url":24,"identifiers":4805},"Muchowski, P. J. & Wacker, J. L. Modulation of neurodegeneration by molecular chaperones. Nature Rev. Neurosci. 6, 11–22 (2005).",{"doi":4806},"10.1038\u002Fnrn1587",{"id":24,"text":4808,"url":24,"identifiers":4809},"Hansson, O. et al. Overexpression of heat shock protein 70 in R6\u002F2 Huntington's disease mice has only modest effects on disease progression. Brain Res. 970, 47–57 (2003).",{"doi":4810},"10.1016\u002FS0006-8993(02)04275-0",{"id":24,"text":4812,"url":24,"identifiers":4813},"Cummings, C. J. et al. Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice. Hum. Mol. Genet. 10, 1511–1518 (2001).",{"doi":4814},"10.1093\u002Fhmg\u002F10.14.1511",{"id":24,"text":4816,"url":24,"identifiers":4817},"Ross, C. A. & Pickart, C. The ubiquitin–proteasome pathway in Parkinson's and other neurodegenerative diseases. Trends Cell Biol. 14, 703–711 (2004).",{"doi":4818},"10.1016\u002Fj.tcb.2004.10.006",{"id":24,"text":4820,"url":24,"identifiers":4821},"Berke, S. J. & Paulson, H. L. Protein aggregation and the ubiquitin–proteasome pathway: gaining the UPPer hand on neurodegeneration. Curr. Opin. Genet. Dev. 13, 253–261 (2003).",{"doi":4822},"10.1016\u002FS0959-437X(03)00053-4",{"id":24,"text":4824,"url":24,"identifiers":4825},"Majeski, A. E. & Dice, J. F. Mechanisms of chaperone-mediated autophagy. Int. J. Biochem. Cell Biol. 36, 2435–2444 (2004).",{"doi":4826},"10.1016\u002Fj.biocel.2004.02.013",{"id":24,"text":4828,"url":24,"identifiers":4829},"Massey, A., Kiffin, R. & Cuervo, A. M. Pathophysiology of chaperone-mediated autophagy. Int. J. Biochem. Cell Biol. 36, 2420–2434 (2004).",{"doi":4830},"10.1016\u002Fj.biocel.2004.04.010",{"id":24,"text":4832,"url":24,"identifiers":4833},"Kiffin, R., Christian, C., Knecht, E. & Cuervo, A. M. Activation of chaperone-mediated autophagy during oxidative stress. Mol. Biol. Cell 15, 4829–4840 (2004).",{"doi":4834},"10.1091\u002Fmbc.e04-06-0477",{"id":24,"text":4836,"url":24,"identifiers":4837},"Cuervo, A. M., Stefanis, L., Fredenburg, R., Lansbury, P. T. & Sulzer, D. Impaired degradation of mutant α-synuclein by chaperone-mediated autophagy. Science 305, 1292–1295 (2004).",{"doi":4838},"10.1126\u002Fscience.1101738",{"id":24,"text":4840,"url":24,"identifiers":4841},"Ravikumar, B. et al. Dynein mutations impair autophagic clearance of aggregate-prone proteins. Nature Genet. 37, 771–776 (2005).",{"doi":4842},"10.1038\u002Fng1591",{"id":24,"text":4844,"url":24,"identifiers":4845},"Johnston, J. A., Ward, C. L. & Kopito, R. R. Aggresomes: a cellular response to misfolded proteins. J. Cell Biol. 143, 1883–1898 (1998).",{"doi":4846},"10.1083\u002Fjcb.143.7.1883",{"id":24,"text":4848,"url":24,"identifiers":4849},"Olanow, C. W., Perl, D. P., DeMartino, G. N. & McNaught, K. S. Lewy-body formation is an aggresome-related process: a hypothesis. Lancet Neurol. 3, 496–503 (2004).",{"doi":4850},"10.1016\u002FS1474-4422(04)00827-0",{"id":24,"text":4852,"url":24,"identifiers":4853},"Iwata, A. et al. Increased susceptibility of cytoplasmic over nuclear polyglutamine aggregates to autophagic degradation. Proc. Natl Acad. Sci. USA (in the press).",{"doi":4854},"10.1073\u002Fpnas.0505801102",{"id":24,"text":4856,"url":24,"identifiers":4857},"Levine, B. Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell 120, 159–162 (2005).",{},{"id":24,"text":4859,"url":24,"identifiers":4860},"Rideout, H. J., Lang-Rollin, I. & Stefanis, L. Involvement of macroautophagy in the dissolution of neuronal inclusions. Int. J. Biochem. Cell Biol. 36, 2551–2562 (2004).",{"doi":4861},"10.1016\u002Fj.biocel.2004.05.008",{"id":24,"text":4863,"url":24,"identifiers":4864},"Fortun, J., Dunn, W. A., Joy, S., Li, J. & Notterpek, L. Emerging role for autophagy in the removal of aggresomes in Schwann cells. J. Neurosci. 23, 10672–10680 (2003).",{"doi":4865},"10.1523\u002FJNEUROSCI.23-33-10672.2003",{"id":24,"text":4867,"url":24,"identifiers":4868},"Qin, Z. H. et al. Autophagy regulates the processing of amino terminal huntingtin fragments. Hum. Mol. Genet. 12, 3231–3244 (2003).",{"doi":4869},"10.1093\u002Fhmg\u002Fddg346",{"id":24,"text":4871,"url":24,"identifiers":4872},"McGeer, P. L. & McGeer, E. G. The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res. Rev. 21, 195–218 (1995).",{"doi":4873},"10.1016\u002F0165-0173(95)00011-9",{"id":24,"text":4875,"url":24,"identifiers":4876},"Yamamoto, A., Lucas, J. J. & Hen, R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 101, 57–66 (2000).",{"doi":4877},"10.1016\u002FS0092-8674(00)80623-6",{"id":24,"text":4879,"url":24,"identifiers":4880},"Martin-Aparicio, E. et al. Proteasomal-dependent aggregate reversal and absence of cell death in a conditional mouse model of Huntington's disease. J. Neurosci. 21, 8772–8781 (2001).",{"doi":4881},"10.1523\u002FJNEUROSCI.21-22-08772.2001",{"id":24,"text":4883,"url":24,"identifiers":4884},"O'Nuallain, B. & Wetzel, R. Conformational Abs recognizing a generic amyloid fibril epitope. Proc. Natl Acad. Sci. USA 99, 1485–1490 (2002).",{"doi":4885},"10.1073\u002Fpnas.022662599",{"id":24,"text":4887,"url":24,"identifiers":4888},"Kayed, R. et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300, 486–489 (2003).",{"doi":4889},"10.1126\u002Fscience.1079469",{"id":24,"text":4891,"url":24,"identifiers":4892},"Tanaka, M., Chien, P., Naber, N., Cooke, R. & Weissman, J. S. Conformational variations in an infectious protein determine prion strain differences. Nature 428, 323–328 (2004).",{"doi":4893},"10.1038\u002Fnature02392",{"id":24,"text":4895,"url":24,"identifiers":4896},"Weissmann, C. Birth of a prion: spontaneous generation revisited. Cell 122, 165–168 (2005).",{"doi":4897},"10.1016\u002Fj.cell.2005.07.001",{"id":24,"text":4899,"url":24,"identifiers":4900},"Serio, T. R. et al. Nucleated conformational conversion and the replication of conformational information by a prion determinant. Science 289, 1317–1321 (2000).",{"doi":4901},"10.1126\u002Fscience.289.5483.1317",{"id":24,"text":4903,"url":24,"identifiers":4904},"Collins, S. R., Douglass, A., Vale, R. D. & Weissman, J. S. Mechanism of prion propagation: amyloid growth occurs by monomer addition. PLoS Biol. 2, e321 (2004).",{"doi":4905},"10.1371\u002Fjournal.pbio.0020321",{"id":24,"text":4907,"url":24,"identifiers":4908},"Williams, A. D. et al. Structural properties of Ab protofibrils stabilized by a small molecule. Proc. Natl Acad. Sci. USA (in the press).",{},{"id":24,"text":4910,"url":24,"identifiers":4911},"McLean, C. A. et al. Soluble pool of Aβ amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann. Neurol. 46, 860–866 (1999).",{"doi":4912},"10.1002\u002F1531-8249(199912)46:6\u003C860::AID-ANA8>3.0.CO;2-M",{"id":24,"text":4914,"url":24,"identifiers":4915},"Lue, L. F. et al. Soluble amyloid-β peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am. J. Pathol. 155, 853–862 (1999).",{"doi":4916},"10.1016\u002FS0002-9440(10)65184-X",{"id":24,"text":4918,"url":24,"identifiers":4919},"Klein, W. L., Krafft, G. A. & Finch, C. E. Targeting small A-β oligomers: the solution to an Alzheimer's disease conundrum? Trends Neurosci. 24, 219–224 (2001).",{"doi":4920},"10.1016\u002FS0166-2236(00)01749-5",{"id":24,"text":4922,"url":24,"identifiers":4923},"Walsh, D. M. et al. Amyloid β-protein fibrillogenesis. structure and biological activity of protofibrillar intermediates. J. Biol. Chem. 274, 25945–25952 (1999).",{"doi":4924},"10.1074\u002Fjbc.274.36.25945",{"id":24,"text":4926,"url":24,"identifiers":4927},"Chromy, B. A. et al. Self-assembly of A-β1–42 into globular neurotoxins. Biochemistry 42, 12749–12760 (2003).",{"doi":4928},"10.1021\u002Fbi030029q",{"id":24,"text":4930,"url":24,"identifiers":4931},"Gong, Y. et al. Alzheimer's disease-affected brain: presence of oligomeric Ab ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc. Natl Acad. Sci. USA 100, 10417–10422 (2003).",{"doi":4932},"10.1073\u002Fpnas.1834302100",{"id":24,"text":4934,"url":24,"identifiers":4935},"Bitan, G. et al. Amyloid β-protein (Ab) assembly: Aβ40 and Aβ42 oligomerize through distinct pathways. Proc. Natl Acad. Sci. USA 100, 330–335 (2003).",{"doi":4936},"10.1073\u002Fpnas.222681699",{"id":24,"text":4938,"url":24,"identifiers":4939},"Walsh, D. M. et al. Naturally secreted oligomers of amyloid b protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535–539 (2002).",{"doi":4940},"10.1038\u002F416535a",{"id":24,"text":4942,"url":24,"identifiers":4943},"Klyubin, I. et al. Amyloid β protein immunotherapy neutralizes Ab oligomers that disrupt synaptic plasticity in vivo. Nature Med. 11, 556–561 (2005).",{"doi":4944},"10.1038\u002Fnm1234",{"id":24,"text":4946,"url":24,"identifiers":4947},"Lashuel, H. A., Hartley, D., Petre, B. M., Walz, T. & Lansbury, P. T. Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature 418, 291 (2002).",{"doi":4948},"10.1038\u002F418291a",{"id":24,"text":4950,"url":24,"identifiers":4951},"Poirier, M. A. et al. Huntingtin spheroids and protofibrils as precursors in polyglutamine fibrilization. J. Biol. Chem. 277, 41032–41037 (2002).",{"doi":4952},"10.1074\u002Fjbc.M205809200",{"id":24,"text":4954,"url":24,"identifiers":4955},"Wacker, J. L., Zareie, M. H., Fong, H., Sarikaya, M. & Muchowski, P. J. Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer. Nature Struct. Mol. Biol. 11, 1215–1222 (2004).",{"doi":4956},"10.1038\u002Fnsmb860",{"id":24,"text":4958,"url":24,"identifiers":4959},"Chen, S., Ferrone, F. A. & Wetzel, R. Huntington's disease age-of-onset linked to polyglutamine aggregation nucleation. Proc. Natl Acad. Sci. USA 99, 11884–11889 (2002).",{"doi":4960},"10.1073\u002Fpnas.182276099",{"id":24,"text":4962,"url":24,"identifiers":4963},"Thakur, A. K. & Wetzel, R. Mutational analysis of the structural organization of polyglutamine aggregates. Proc. Natl Acad. Sci. USA 99, 17014–17019 (2002).",{"doi":4964},"10.1073\u002Fpnas.252523899",{"id":24,"text":4966,"url":24,"identifiers":4967},"Poirier, M. A., Jiang, H. & Ross, C. A. A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity: evidence for a compact beta-sheet structure. Hum. Mol. Genet. 14, 765–774 (2005).",{"doi":4968},"10.1093\u002Fhmg\u002Fddi071",{"id":24,"text":4970,"url":24,"identifiers":4971},"Selkoe, D. J. Alzheimer disease: mechanistic understanding predicts novel therapies. Ann. Intern. Med. 140, 627–638 (2004).",{"doi":4972},"10.7326\u002F0003-4819-140-8-200404200-00047",{"id":24,"text":4974,"url":24,"identifiers":4975},"Bence, N. F., Sampat, R. M. & Kopito, R. R. Impairment of the ubiquitin–proteasome system by protein aggregation. Science 292, 1552–1555 (2001).",{"doi":4976},"10.1126\u002Fscience.292.5521.1552",{"id":24,"text":4978,"url":24,"identifiers":4979},"Venkatraman, P., Wetzel, R., Tanaka, M., Nukina, N. & Goldberg, A. L. Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins. Mol. Cell 14, 95–104 (2004).",{"doi":4980},"10.1016\u002FS1097-2765(04)00151-0",{"id":24,"text":4982,"url":24,"identifiers":4983},"Verhoef, L. G., Lindsten, K., Masucci, M. G. & Dantuma, N. P. Aggregate formation inhibits proteasomal degradation of polyglutamine proteins. Hum. Mol. Genet. 11, 2689–2700 (2002).",{"doi":4984},"10.1093\u002Fhmg\u002F11.22.2689",{"id":24,"text":4986,"url":24,"identifiers":4987},"Jana, N. R., Zemskov, E. A., Wang, G. & Nukina, N. Altered proteasomal function due to the expression of polyglutamine-expanded truncated N-terminal huntingtin induces apoptosis by caspase activation through mitochondrial cytochrome c release. Hum. Mol. Genet. 10, 1049–1059 (2001).",{"doi":4988},"10.1093\u002Fhmg\u002F10.10.1049",{"id":24,"text":4990,"url":24,"identifiers":4991},"Bennett, E. J., Bence, N. F., Jayakumar, R. & Kopito, R. R. Global impairment of the ubiquitin–proteasome system by nuclear or cytoplasmic protein aggregates precedes inclusion body formation. Mol. Cell 17, 351–365 (2005).",{"doi":4992},"10.1016\u002Fj.molcel.2004.12.021",{"id":24,"text":4994,"url":24,"identifiers":4995},"Bowman, A. B., Yoo, S. Y., Dantuma, N. P. & Zoghbi, H. Y. Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin–proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation. Hum. Mol. Genet. 14, 679–691 (2005).",{"doi":4996},"10.1093\u002Fhmg\u002Fddi064",{"id":24,"text":4998,"url":24,"identifiers":4999},"McNaught, K. S., Perl, D. P., Brownell, A. L. & Olanow, C. W. Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease. Ann. Neurol. 56, 149–162 (2004).",{"doi":5000},"10.1002\u002Fana.20186",{"id":24,"text":5002,"url":24,"identifiers":5003},"McCampbell, A. et al. CREB-binding protein sequestration by expanded polyglutamine. Hum. Mol. Genet. 9, 2197–2202 (2000).",{"doi":5004},"10.1093\u002Fhmg\u002F9.14.2197",{"id":24,"text":5006,"url":24,"identifiers":5007},"Preisinger, E., Jordan, B. M., Kazantsev, A. & Housman, D. Evidence for a recruitment and sequestration mechanism in Huntington's disease. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 354, 1029–1034 (1999).",{"doi":5008},"10.1098\u002Frstb.1999.0455",{"id":24,"text":5010,"url":24,"identifiers":5011},"Kazantsev, A., Preisinger, E., Dranovsky, A., Goldgaber, D. & Housman, D. Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells. Proc. Natl Acad. Sci. USA 96, 11404–11409 (1999).",{"doi":5012},"10.1073\u002Fpnas.96.20.11404",{"id":24,"text":5014,"url":24,"identifiers":5015},"Nucifora, F. C., Jr. et al. Interference by huntingtin and atrophin-1 with CBP-mediated transcription leading to cellular toxicity. Science 291, 2423–2428 (2001).",{"doi":5016},"10.1126\u002Fscience.1056784",{"id":24,"text":5018,"url":24,"identifiers":5019},"Chen, S., Berthelier, V., Yang, W. & Wetzel, R. Polyglutamine aggregation behavior in vitro supports a recruitment mechanism of cytotoxicity. J. Mol. Biol. 311, 173–182 (2001).",{"doi":5020},"10.1006\u002Fjmbi.2001.4850",{"id":24,"text":5022,"url":24,"identifiers":5023},"Quist, A. et al. Amyloid ion channels: A common structural link for protein-misfolding disease. Proc. Natl Acad. Sci. USA 102, 10427–10432 (2005).",{"doi":5024},"10.1073\u002Fpnas.0502066102",{"id":24,"text":5026,"url":24,"identifiers":5027},"Ross, C. A. et al. Huntington disease and the related disorder, dentatorubral-pallidoluysian atrophy (DRPLA). Medicine (Baltimore) 76, 305–338 (1997).",{"doi":5028},"10.1097\u002F00005792-199709000-00001",{"id":24,"text":5030,"url":24,"identifiers":5031},"Wanker, E. E. Protein aggregation and pathogenesis of Huntington's disease: mechanisms and correlations. Biol. Chem. 381, 937–942 (2000).",{"doi":5032},"10.1515\u002FBC.2000.114",{"id":24,"text":5034,"url":24,"identifiers":5035},"Hardy, J. Toward Alzheimer therapies based on genetic knowledge. Annu. Rev. Med. 55, 15–25 (2004).",{"doi":5036},"10.1146\u002Fannurev.med.55.091902.103607",{"id":24,"text":5038,"url":24,"identifiers":5039},"Wood, J. D., Beaujeux, T. P. & Shaw, P. J. Protein aggregation in motor neurone disorders. Neuropathol. Appl. Neurobiol. 29, 529–545 (2003).",{"doi":5040},"10.1046\u002Fj.0305-1846.2003.00518.x",{"id":24,"text":5042,"url":24,"identifiers":5043},"Chien, P., Weissman, J. S. & DePace, A. H. Emerging principles of conformation-based prion inheritance. Annu. Rev. Biochem. 73, 617–656 (2004).",{"doi":5044},"10.1146\u002Fannurev.biochem.72.121801.161837",{"id":24,"text":5046,"url":24,"identifiers":5047},"Revesz, T. et al. Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view. J. Neuropathol. Exp. Neurol. 62, 885–898 (2003).",{"doi":5048},"10.1093\u002Fjnen\u002F62.9.885",{"id":24,"text":5050,"url":24,"identifiers":5051},"Hedera, P. & Turner, R. S. Inherited dementias. Neurol. Clin. 20, 779–808 (2002).",{"doi":5052},"10.1016\u002FS0733-8619(01)00020-2",{"id":5054,"createTime":5055,"updateTime":5055,"relativeEntities":5056,"slug":5057,"properties":5058,"entityType":131,"verifyStatus":132,"verifyTime":5055,"verifyNote":133,"languages":5071,"translateLanguages":24,"viewCount":25,"primaryUrl":5072,"fullTextUrl":24,"authors":5073,"publicationType":174,"publisherRelationship":5112,"citationCount":5166,"citationInfo":5167,"publishDate":5175,"publishYear":5168,"citationAnalyzeStatus":23,"lastCitationAnalyze":24,"indexDatabases":5176,"openAccess":24,"references":5177,"isForceReanalyzing":409},"d87830b4-f073-428f-94a8-0e171abd3de0","2025-02-08T17:28:25.799+00:00",[],"Advances-in-protein-structure-prediction-and-design",{"openalex":5059,"mag":5061,"title":5063,"pm":5065,"doi":5067,"pmc":5069},{"VOID":5060},"W2968494487",{"VOID":5062},"2968494487",{"EN":5064},"Advances in protein structure prediction and design",{"VOID":5066},"31417196",{"VOID":5068},"10.1038\u002Fs41580-019-0163-x",{"VOID":5070},"7032036",[135],"https:\u002F\u002Fwww.nature.com\u002Farticles\u002Fs41580-019-0163-x",[5074,5093],{"id":5075,"sortIndex":25,"researcher":24,"roles":5076,"affiliations":5077,"properties":5086,"displayName":5090,"givenName":24,"familyName":24},"871bfd40-f430-4590-a419-6b57443e2021",[],[5078],{"id":5079,"sortIndex":25,"affiliation":5080,"properties":24},"55dc3925-1494-4816-9d3e-d30968169bf7",{"id":5079,"createTime":24,"updateTime":24,"relativeEntities":5081,"slug":24,"properties":5082,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":5085,"statistic":24},[],{"title":5083},{"VI":5084},"Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA",[],{"orcid":5087,"title":5089,"openalex":5091},{"VOID":5088},"https:\u002F\u002Forcid.org\u002F0000-0003-4907-9699",{"EN":5090},"Brian Kuhlman",{"VOID":5092},"A5013989048",{"id":5094,"sortIndex":99,"researcher":24,"roles":5095,"affiliations":5096,"properties":5105,"displayName":5109,"givenName":24,"familyName":24},"e93840af-3a5c-4abf-852f-31803101b329",[],[5097],{"id":5098,"sortIndex":25,"affiliation":5099,"properties":24},"1b42c538-5ab3-4250-807d-e4281aa6cdb5",{"id":5098,"createTime":24,"updateTime":24,"relativeEntities":5100,"slug":24,"properties":5101,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":5104,"statistic":24},[],{"title":5102},{"EN":5103},"Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA",[],{"orcid":5106,"title":5108,"openalex":5110},{"VOID":5107},"https:\u002F\u002Forcid.org\u002F0000-0002-0224-6464",{"EN":5109},"Philip Bradley",{"VOID":5111},"A5067744380",{"url":24,"publisher":5113,"properties":5160},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":5114,"slug":10,"properties":5115,"entityType":22,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":25,"subjectFields":5120,"manageAffiliations":5129,"indexDatabases":5140,"url":90,"thumbnailPath":24,"statistic":5155,"gsStatistic":24,"type":24,"analyzePriority":24},[],{"country":5116,"eissn":5117,"issn":5118,"title":5119},{"VOID":13},{"VOID":15},{"VOID":17},{"EN":19},[5121,5125],{"id":28,"createTime":24,"updateTime":24,"relativeEntities":5122,"label":5123,"description":5124,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":31},{},{"id":34,"createTime":24,"updateTime":24,"relativeEntities":5126,"label":5127,"description":5128,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":37},{},[5130,5135],{"id":41,"createTime":24,"updateTime":24,"relativeEntities":5131,"slug":24,"properties":5132,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":5134,"statistic":24},[],{"title":5133},{"EN":45},[],{"id":48,"createTime":24,"updateTime":24,"relativeEntities":5136,"slug":24,"properties":5137,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":5139,"statistic":24},[],{"title":5138},{"EN":52},[],[5141,5148],{"id":56,"indexDatabase":5142,"url":69,"indexYears":24,"academicFieldIds":5147,"indexDatabaseRanking":24},{"id":58,"createTime":24,"updateTime":24,"relativeEntities":5143,"label":5144,"description":5145,"key":65,"publicationTags":5146,"standard":24},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":5149,"url":84,"indexYears":85,"academicFieldIds":5154,"indexDatabaseRanking":89},{"id":75,"createTime":24,"updateTime":24,"relativeEntities":5150,"label":5151,"description":5152,"key":81,"publicationTags":5153,"standard":24},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88],{"impactFactor":25,"impactFactorByYear":5156,"i10Index":97,"i10IndexLast5Year":25,"totalPublication":97,"totalPublicationByYear":5157,"totalCitation":100,"totalCitationByYear":5158,"totalCitationPerPublication":106,"totalCitationPerPublicationByYear":5159,"hindexLast5Year":97,"hindex":97},{"2016":93,"2017":94,"2019":95,"2020":96},{"2007":99,"2009":99,"2015":99,"2018":99},{"2007":102,"2009":103,"2015":104,"2018":105},{"2007":102,"2009":103,"2015":104,"2018":105},{"issue":5161,"pages":5162,"volume":5164},{"VOID":1791},{"VOID":5163},"681-697",{"VOID":5165},"20",681,{"total":5166,"publishYear":5168,"statisticByYear":5169},2019,{"2019":5170,"2020":1117,"2021":5171,"2022":5172,"2023":5173,"2024":5174,"2025":97},5,146,144,165,151,"2019-11-01",[67,89],[5178,5182,5186,5190,5194,5198,5202,5206,5210,5214,5218,5222,5226,5230,5234,5238,5242,5246,5250,5254,5258,5262,5265,5269,5273,5277,5281,5285,5289,5293,5297,5301,5305,5309,5313,5317,5321,5325,5329,5333,5337,5341,5345,5349,5353,5357,5361,5365,5369,5373,5377,5381,5385,5389,5393,5397,5401,5405,5409,5413,5417,5421,5425,5429,5433,5437,5441,5445,5449,5452,5456,5460,5464,5468,5472,5476,5480,5484,5488,5492,5496,5500,5504,5508,5512,5516,5520,5524,5528,5532,5536,5540,5544,5548,5552,5556,5560,5564,5568,5572,5576,5580,5584,5588,5592,5596,5600,5604,5608,5612,5616,5620,5624,5628,5631,5635,5639,5643,5647,5651,5655,5659,5663,5667,5671,5675,5679,5683,5687,5691,5695,5699,5703,5707,5711,5715,5719,5723,5727,5731,5735,5739,5743,5747,5751,5755,5759,5763,5767,5771,5775,5779,5783,5787,5791,5795,5799,5803,5807,5811,5815,5819,5823,5827,5831,5835,5839,5843,5847,5851,5855,5859],{"id":24,"text":5179,"url":24,"identifiers":5180},"Jones, D. T., Singh, T., Kosciolek, T. & Tetchner, S. MetaPSICOV: combining coevolution methods for accurate prediction of contacts and long range hydrogen bonding in proteins. Bioinformatics 31, 999–1006 (2015).",{"doi":5181},"10.1093\u002Fbioinformatics\u002Fbtu791",{"id":24,"text":5183,"url":24,"identifiers":5184},"Wang, S., Sun, S., Li, Z., Zhang, R. & Xu, J. Accurate de novo prediction of protein contact map by ultra-deep learning model. PLoS Comput. Biol. 13, e1005324 (2017). This paper presents an accurate deep learning method that predicts residue–residue contacts by integrating 1D sequence features with 2D residue covariation and pairwise interaction features.",{"doi":5185},"10.1371\u002Fjournal.pcbi.1005324",{"id":24,"text":5187,"url":24,"identifiers":5188},"Huang, J. et al. CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nat. Methods 14, 71–73 (2017).",{"doi":5189},"10.1038\u002Fnmeth.4067",{"id":24,"text":5191,"url":24,"identifiers":5192},"Park, H. et al. Simultaneous optimization of biomolecular energy functions on features from small molecules and macromolecules. J. Chem. Theory Comput. 12, 6201–6212 (2016).",{"doi":5193},"10.1021\u002Facs.jctc.6b00819",{"id":24,"text":5195,"url":24,"identifiers":5196},"Heo, L. & Feig, M. Experimental accuracy in protein structure refinement via molecular dynamics simulations. Proc. Natl Acad. Sci. USA 115, 13276–13281 (2018).",{"doi":5197},"10.1073\u002Fpnas.1811364115",{"id":24,"text":5199,"url":24,"identifiers":5200},"Park, H., Ovchinnikov, S., Kim, D. E., DiMaio, F. & Baker, D. Protein homology model refinement by large-scale energy optimization. Proc. Natl Acad. Sci. USA 115, 3054–3059 (2018). Heo et al. and Park et al. report substantial progress in refinement of protein structure models by physics-based simulations.",{"doi":5201},"10.1073\u002Fpnas.1719115115",{"id":24,"text":5203,"url":24,"identifiers":5204},"Mravic, M. et al. Packing of apolar side chains enables accurate design of highly stable membrane proteins. Science 363, 1418–1423 (2019). This study reports on the design of helical membrane proteins with only apolar interactions between side chains, which demonstrates that hydrogen bonding between helices is not required for the folding and stability of membrane proteins.",{"doi":5205},"10.1126\u002Fscience.aav7541",{"id":24,"text":5207,"url":24,"identifiers":5208},"Dou, J. et al. De novo design of a fluorescence-activating β-barrel. Nature 561, 485–491 (2018). The first de novo design of a functional β-barrel protein, which reveals that symmetry breaking within the barrel is required to eliminate backbone strain and maximize hydrogen bonding between β-strands.",{"doi":5209},"10.1038\u002Fs41586-018-0509-0",{"id":24,"text":5211,"url":24,"identifiers":5212},"Silva, D.-A. et al. De novo design of potent and selective mimics of IL-2 and IL-15. Nature 565, 186–191 (2019).",{"doi":5213},"10.1038\u002Fs41586-018-0830-7",{"id":24,"text":5215,"url":24,"identifiers":5216},"Chen, I.-M. A. et al. IMG\u002FM: integrated genome and metagenome comparative data analysis system. Nucleic Acids Res. 45, D507–D516 (2017).",{"doi":5217},"10.1093\u002Fnar\u002Fgkw929",{"id":24,"text":5219,"url":24,"identifiers":5220},"Berman, H. M. et al. The protein data bank. Nucleic Acids Res. 28, 235–242 (2000).",{"doi":5221},"10.1093\u002Fnar\u002F28.1.235",{"id":24,"text":5223,"url":24,"identifiers":5224},"LeCun, Y., Bengio, Y. & Hinton, G. Deep learning. Nature 521, 436–444 (2015).",{"doi":5225},"10.1038\u002Fnature14539",{"id":24,"text":5227,"url":24,"identifiers":5228},"Anson, M. L. & Mirsky, A. E. Protein coagulation and its reversal: the preparation of insoluble globin, soluble globin and heme. J. Gen. Physiol. 13, 469–476 (1930).",{"doi":5229},"10.1085\u002Fjgp.13.4.469",{"id":24,"text":5231,"url":24,"identifiers":5232},"Lumry, R. & Eyring, H. Conformation changes of proteins. J. Phys. Chem. 58, 110–120 (1954).",{"doi":5233},"10.1021\u002Fj150512a005",{"id":24,"text":5235,"url":24,"identifiers":5236},"Anfinsen, C. B., Haber, E., Sela, M. & White, F. H. Jr The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain. Proc. Natl Acad. Sci. USA 47, 1309–1314 (1961).",{"doi":5237},"10.1073\u002Fpnas.47.9.1309",{"id":24,"text":5239,"url":24,"identifiers":5240},"Anfinsen, C. B. Principles that govern the folding of protein chains. Science 181, 223–230 (1973).",{"doi":5241},"10.1126\u002Fscience.181.4096.223",{"id":24,"text":5243,"url":24,"identifiers":5244},"Anfinsen, C. B. & Scheraga, H. A. Experimental and theoretical aspects of protein folding. Adv. Protein Chem. 29, 205–300 (1975).",{"doi":5245},"10.1016\u002FS0065-3233(08)60413-1",{"id":24,"text":5247,"url":24,"identifiers":5248},"Lazaridis, T. & Karplus, M. Effective energy functions for protein structure prediction. Curr. Opin. Struct. Biol. 10, 139–145 (2000).",{"doi":5249},"10.1016\u002FS0959-440X(00)00063-4",{"id":24,"text":5251,"url":24,"identifiers":5252},"Dill, K. A., Ozkan, S. B., Shell, M. S. & Weikl, T. R. The protein folding problem. Annu. Rev. Biophys. 37, 289–316 (2008).",{"doi":5253},"10.1146\u002Fannurev.biophys.37.092707.153558",{"id":24,"text":5255,"url":24,"identifiers":5256},"Karplus, M. The levinthal paradox: yesterday and today. Fold. Des. 2, S69–75 (1997).",{"doi":5257},"10.1016\u002FS1359-0278(97)00067-9",{"id":24,"text":5259,"url":24,"identifiers":5260},"Levitt, M. & Warshel, A. Computer simulation of protein folding. Nature 253, 694–698 (1975).",{"doi":5261},"10.1038\u002F253694a0",{"id":24,"text":5263,"url":24,"identifiers":5264},"Levinthal, C. How to fold graciously. Mossbauer Spectrosc. Biol. Syst. 67, 22–24 (1969).",{},{"id":24,"text":5266,"url":24,"identifiers":5267},"Bryngelson, J. D., Onuchic, J. N., Socci, N. D. & Wolynes, P. G. Funnels, pathways, and the energy landscape of protein folding: a synthesis. Proteins 21, 167–195 (1995).",{"doi":5268},"10.1002\u002Fprot.340210302",{"id":24,"text":5270,"url":24,"identifiers":5271},"Dill, K. A. Dominant forces in protein folding. Biochemistry 29, 7133–7155 (1990).",{"doi":5272},"10.1021\u002Fbi00483a001",{"id":24,"text":5274,"url":24,"identifiers":5275},"Monticelli, L. et al. The MARTINI coarse-grained force field: extension to proteins. J. Chem. Theory Comput. 4, 819–834 (2008).",{"doi":5276},"10.1021\u002Fct700324x",{"id":24,"text":5278,"url":24,"identifiers":5279},"Tozzini, V. Coarse-grained models for proteins. Curr. Opin. Struct. Biol. 15, 144–150 (2005).",{"doi":5280},"10.1016\u002Fj.sbi.2005.02.005",{"id":24,"text":5282,"url":24,"identifiers":5283},"Maisuradze, G. G., Senet, P., Czaplewski, C., Liwo, A. & Scheraga, H. A. Investigation of protein folding by coarse-grained molecular dynamics with the UNRES force field. J. Phys. Chem. A 114, 4471–4485 (2010).",{"doi":5284},"10.1021\u002Fjp9117776",{"id":24,"text":5286,"url":24,"identifiers":5287},"Altschul, S. F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997).",{"doi":5288},"10.1093\u002Fnar\u002F25.17.3389",{"id":24,"text":5290,"url":24,"identifiers":5291},"Eddy, S. R. Profile hidden Markov models. Bioinformatics 14, 755–763 (1998).",{"doi":5292},"10.1093\u002Fbioinformatics\u002F14.9.755",{"id":24,"text":5294,"url":24,"identifiers":5295},"Remmert, M., Biegert, A., Hauser, A. & Söding, J. HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment. Nat. Methods 9, 173–175 (2011).",{"doi":5296},"10.1038\u002Fnmeth.1818",{"id":24,"text":5298,"url":24,"identifiers":5299},"Sadreyev, R. & Grishin, N. COMPASS: a tool for comparison of multiple protein alignments with assessment of statistical significance. J. Mol. Biol. 326, 317–336 (2003).",{"doi":5300},"10.1016\u002FS0022-2836(02)01371-2",{"id":24,"text":5302,"url":24,"identifiers":5303},"Söding, J. Protein homology detection by HMM–HMM comparison. Bioinformatics 21, 951–960 (2005).",{"doi":5304},"10.1093\u002Fbioinformatics\u002Fbti125",{"id":24,"text":5306,"url":24,"identifiers":5307},"Bowie, J. U., Lüthy, R. & Eisenberg, D. A method to identify protein sequences that fold into a known three-dimensional structure. Science 253, 164–170 (1991).",{"doi":5308},"10.1126\u002Fscience.1853201",{"id":24,"text":5310,"url":24,"identifiers":5311},"Jones, D. T., Taylor, W. R. & Thornton, J. M. A new approach to protein fold recognition. Nature 358, 86–89 (1992).",{"doi":5312},"10.1038\u002F358086a0",{"id":24,"text":5314,"url":24,"identifiers":5315},"Waterhouse, A. et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46, W296–W303 (2018).",{"doi":5316},"10.1093\u002Fnar\u002Fgky427",{"id":24,"text":5318,"url":24,"identifiers":5319},"Krivov, G. G., Shapovalov, M. V. & Dunbrack, R. L. Improved prediction of protein side-chain conformations with SCWRL4. Proteins: Struct. Funct. Bioinf. 77, 778–795 (2009).",{"doi":5320},"10.1002\u002Fprot.22488",{"id":24,"text":5322,"url":24,"identifiers":5323},"Webb, B. & Sali, A. Protein structure modeling with MODELLER. Methods Mol. Biol. 1654, 39–54 (2017).",{"doi":5324},"10.1007\u002F978-1-4939-7231-9_4",{"id":24,"text":5326,"url":24,"identifiers":5327},"Yang, J. et al. The I-TASSER Suite: protein structure and function prediction. Nat. Methods 12, 7–8 (2015).",{"doi":5328},"10.1038\u002Fnmeth.3213",{"id":24,"text":5330,"url":24,"identifiers":5331},"Song, Y. et al. High-resolution comparative modeling with RosettaCM. Structure 21, 1735–1742 (2013).",{"doi":5332},"10.1016\u002Fj.str.2013.08.005",{"id":24,"text":5334,"url":24,"identifiers":5335},"Ovchinnikov, S. et al. Protein structure determination using metagenome sequence data. Science 355, 294–298 (2017). This study shows that inclusion of sequence data from metagenomics triples the number of protein families for which accurate structural models can be built using folding simulations that incorporate covariation-derived residue–residue contact predictions.",{"doi":5336},"10.1126\u002Fscience.aah4043",{"id":24,"text":5338,"url":24,"identifiers":5339},"Jones, D. T. & McGuffin, L. J. Assembling novel protein folds from super-secondary structural fragments. Proteins 53, 480–485 (2003).",{"doi":5340},"10.1002\u002Fprot.10542",{"id":24,"text":5342,"url":24,"identifiers":5343},"Simons, K. T., Kooperberg, C., Huang, E. & Baker, D. Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and Bayesian scoring functions. J. Mol. Biol. 268, 209–225 (1997).",{"doi":5344},"10.1006\u002Fjmbi.1997.0959",{"id":24,"text":5346,"url":24,"identifiers":5347},"Xu, D. & Zhang, Y. Ab initio protein structure assembly using continuous structure fragments and optimized knowledge-based force field. Proteins 80, 1715–1735 (2012).",{"doi":5348},"10.1002\u002Fprot.24105",{"id":24,"text":5350,"url":24,"identifiers":5351},"Metropolis, N., Rosenbluth, A. W., Rosenbluth, M. N., Teller, A. H. & Teller, E. Equation of state calculations by fast computing machines. J. Chem. Phys. 21, 1087–1092 (1953).",{"doi":5352},"10.1063\u002F1.1699114",{"id":24,"text":5354,"url":24,"identifiers":5355},"Jones, T. A. & Thirup, S. Using known substructures in protein model building and crystallography. EMBO J. 5, 819–822 (1986).",{"doi":5356},"10.1002\u002Fj.1460-2075.1986.tb04287.x",{"id":24,"text":5358,"url":24,"identifiers":5359},"Baeten, L. et al. Reconstruction of protein backbones from the BriX collection of canonical protein fragments. PLoS Comput. Biol. 4, e1000083 (2008).",{"doi":5360},"10.1371\u002Fjournal.pcbi.1000083",{"id":24,"text":5362,"url":24,"identifiers":5363},"Bystroff, C., Simons, K. T., Han, K. F. & Baker, D. Local sequence–structure correlations in proteins. Curr. Opin. Biotechnol. 7, 417–421 (1996).",{"doi":5364},"10.1016\u002FS0958-1669(96)80117-0",{"id":24,"text":5366,"url":24,"identifiers":5367},"Bujnicki, J. M. Protein-structure prediction by recombination of fragments. Chembiochem. 7, 19–27 (2006).",{"doi":5368},"10.1002\u002Fcbic.200500235",{"id":24,"text":5370,"url":24,"identifiers":5371},"Leaver-Fay, A. et al. ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules. Methods Enzymol. 487, 545–574 (2011).",{"doi":5372},"10.1016\u002FB978-0-12-381270-4.00019-6",{"id":24,"text":5374,"url":24,"identifiers":5375},"Moult, J., Pedersen, J. T., Judson, R. & Fidelis, K. A large-scale experiment to assess protein structure prediction methods. Proteins: Struct. Funct. Bioinf. 23, ii–iv (1995).",{"doi":5376},"10.1002\u002Fprot.340230303",{"id":24,"text":5378,"url":24,"identifiers":5379},"Atchley, W. R., Wollenberg, K. R., Fitch, W. M., Terhalle, W. & Dress, A. W. Correlations among amino acid sites in bHLH protein domains: an information theoretic analysis. Mol. Biol. Evol. 17, 164–178 (2000).",{"doi":5380},"10.1093\u002Foxfordjournals.molbev.a026229",{"id":24,"text":5382,"url":24,"identifiers":5383},"Fodor, A. A. & Aldrich, R. W. Influence of conservation on calculations of amino acid covariance in multiple sequence alignments. Proteins 56, 211–221 (2004).",{"doi":5384},"10.1002\u002Fprot.20098",{"id":24,"text":5386,"url":24,"identifiers":5387},"Weigt, M., White, R. A., Szurmant, H., Hoch, J. A. & Hwa, T. Identification of direct residue contacts in protein-protein interaction by message passing. Proc. Natl Acad. Sci. USA 106, 67–72 (2009).",{"doi":5388},"10.1073\u002Fpnas.0805923106",{"id":24,"text":5390,"url":24,"identifiers":5391},"Morcos, F. et al. Direct-coupling analysis of residue coevolution captures native contacts across many protein families. Proc. Natl Acad. Sci. USA 108, E1293–301 (2011).",{"doi":5392},"10.1073\u002Fpnas.1111471108",{"id":24,"text":5394,"url":24,"identifiers":5395},"Balakrishnan, S., Kamisetty, H., Carbonell, J. G., Lee, S.-I. & Langmead, C. J. Learning generative models for protein fold families. Proteins 79, 1061–1078 (2011).",{"doi":5396},"10.1002\u002Fprot.22934",{"id":24,"text":5398,"url":24,"identifiers":5399},"Jones, D. T., Buchan, D. W. A., Cozzetto, D. & Pontil, M. PSICOV: precise structural contact prediction using sparse inverse covariance estimation on large multiple sequence alignments. Bioinformatics 28, 184–190 (2012).",{"doi":5400},"10.1093\u002Fbioinformatics\u002Fbtr638",{"id":24,"text":5402,"url":24,"identifiers":5403},"Nugent, T. & Jones, D. T. Accurate de novo structure prediction of large transmembrane protein domains using fragment-assembly and correlated mutation analysis. Proc. Natl Acad. Sci. USA 109, E1540–E1547 (2012).",{"doi":5404},"10.1073\u002Fpnas.1120036109",{"id":24,"text":5406,"url":24,"identifiers":5407},"Ovchinnikov, S. et al. Large-scale determination of previously unsolved protein structures using evolutionary information. eLife 4, e09248 (2015).",{"doi":5408},"10.7554\u002FeLife.09248",{"id":24,"text":5410,"url":24,"identifiers":5411},"Zhang, C., Mortuza, S. M., He, B., Wang, Y. & Zhang, Y. Template-based and free modeling of I-TASSER and QUARK pipelines using predicted contact maps in CASP12. Proteins 86, 136–151 (2018).",{"doi":5412},"10.1002\u002Fprot.25414",{"id":24,"text":5414,"url":24,"identifiers":5415},"Marks, D. S. et al. Protein 3D structure computed from evolutionary sequence variation. PLoS ONE 6, e28766 (2011).",{"doi":5416},"10.1371\u002Fjournal.pone.0028766",{"id":24,"text":5418,"url":24,"identifiers":5419},"Brünger, A. T. et al. Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr. D Biol. Crystallogr. 54, 905–921 (1998).",{"doi":5420},"10.1107\u002FS0907444998003254",{"id":24,"text":5422,"url":24,"identifiers":5423},"Hopf, T. A. et al. Three-dimensional structures of membrane proteins from genomic sequencing. Cell 149, 1607–1621 (2012).",{"doi":5424},"10.1016\u002Fj.cell.2012.04.012",{"id":24,"text":5426,"url":24,"identifiers":5427},"Toth-Petroczy, A. et al. Structured states of disordered proteins from genomic sequences. Cell 167, 158–170.e12 (2016).",{"doi":5428},"10.1016\u002Fj.cell.2016.09.010",{"id":24,"text":5430,"url":24,"identifiers":5431},"Cheng, J., Randall, A. Z., Sweredoski, M. J. & Baldi, P. SCRATCH: a protein structure and structural feature prediction server. Nucleic Acids Res. 33, W72–W76 (2005).",{"doi":5432},"10.1093\u002Fnar\u002Fgki396",{"id":24,"text":5434,"url":24,"identifiers":5435},"Shen, Y. & Bax, A. Protein backbone and sidechain torsion angles predicted from NMR chemical shifts using artificial neural networks. J. Biomol. NMR 56, 227–241 (2013).",{"doi":5436},"10.1007\u002Fs10858-013-9741-y",{"id":24,"text":5438,"url":24,"identifiers":5439},"Faraggi, E., Zhang, T., Yang, Y., Kurgan, L. & Zhou, Y. SPINE X: improving protein secondary structure prediction by multistep learning coupled with prediction of solvent accessible surface area and backbone torsion angles. J. Comput. Chem. 33, 259–267 (2012).",{"doi":5440},"10.1002\u002Fjcc.21968",{"id":24,"text":5442,"url":24,"identifiers":5443},"Jones, D. T. Protein secondary structure prediction based on position-specific scoring matrices. J. Mol. Biol. 292, 195–202 (1999).",{"doi":5444},"10.1006\u002Fjmbi.1999.3091",{"id":24,"text":5446,"url":24,"identifiers":5447},"Karplus, K. SAM-T08, HMM-based protein structure prediction. Nucleic Acids Res. 37, W492–W497 (2009).",{"doi":5448},"10.1093\u002Fnar\u002Fgkp403",{"id":24,"text":5450,"url":24,"identifiers":5451},"Krizhevsky, A., Sutskever, I. & Hinton, G. E. Imagenet classification with deep convolutional neural networks. Adv. Neural Inf. Process. Syst. 25, 1097–1105 (2012).",{},{"id":24,"text":5453,"url":24,"identifiers":5454},"Liu, Y., Palmedo, P., Ye, Q., Berger, B. & Peng, J. Enhancing evolutionary couplings with deep convolutional neural networks. Cell Syst. 6, 65–74.e3 (2018).",{"doi":5455},"10.1016\u002Fj.cels.2017.11.014",{"id":24,"text":5457,"url":24,"identifiers":5458},"Jones, D. T. & Kandathil, S. M. High precision in protein contact prediction using fully convolutional neural networks and minimal sequence features. Bioinformatics 34, 3308–3315 (2018).",{"doi":5459},"10.1093\u002Fbioinformatics\u002Fbty341",{"id":24,"text":5461,"url":24,"identifiers":5462},"Huang, P.-S., Boyken, S. E. & Baker, D. The coming of age of de novo protein design. Nature 537, 320–327 (2016).",{"doi":5463},"10.1038\u002Fnature19946",{"id":24,"text":5465,"url":24,"identifiers":5466},"Khoury, G. A., Smadbeck, J., Kieslich, C. A. & Floudas, C. A. Protein folding and de novo protein design for biotechnological applications. Trends Biotechnol. 32, 99–109 (2014).",{"doi":5467},"10.1016\u002Fj.tibtech.2013.10.008",{"id":24,"text":5469,"url":24,"identifiers":5470},"Woolfson, D. N. et al. De novo protein design: how do we expand into the universe of possible protein structures? Curr. Opin. Struct. Biol. 33, 16–26 (2015).",{"doi":5471},"10.1016\u002Fj.sbi.2015.05.009",{"id":24,"text":5473,"url":24,"identifiers":5474},"Coluzza, I. Computational protein design: a review. J. Phys. Condens. Matter 29, 143001 (2017).",{"doi":5475},"10.1088\u002F1361-648X\u002Faa5c76",{"id":24,"text":5477,"url":24,"identifiers":5478},"Mackenzie, C. O. & Grigoryan, G. Protein structural motifs in prediction and design. Curr. Opin. Struct. Biol. 44, 161–167 (2017).",{"doi":5479},"10.1016\u002Fj.sbi.2017.03.012",{"id":24,"text":5481,"url":24,"identifiers":5482},"Kuhlman, B. et al. Design of a novel globular protein fold with atomic-level accuracy. Science 302, 1364–1368 (2003).",{"doi":5483},"10.1126\u002Fscience.1089427",{"id":24,"text":5485,"url":24,"identifiers":5486},"Brunette, T. J. et al. Exploring the repeat protein universe through computational protein design. Nature 528, 580–584 (2015).",{"doi":5487},"10.1038\u002Fnature16162",{"id":24,"text":5489,"url":24,"identifiers":5490},"Huang, P.-S. et al. De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy. Nat. Chem. Biol. 12, 29–34 (2016).",{"doi":5491},"10.1038\u002Fnchembio.1966",{"id":24,"text":5493,"url":24,"identifiers":5494},"Doyle, L. et al. Rational design of α-helical tandem repeat proteins with closed architectures. Nature 528, 585–588 (2015). First de novo design of repeat proteins that adopt ‘doughnut’-like structures with the N and C termini adjacent in three-dimensional space.",{"doi":5495},"10.1038\u002Fnature16191",{"id":24,"text":5497,"url":24,"identifiers":5498},"Marcos, E. et al. Principles for designing proteins with cavities formed by curved β sheets. Science 355, 201–206 (2017).",{"doi":5499},"10.1126\u002Fscience.aah7389",{"id":24,"text":5501,"url":24,"identifiers":5502},"Marcos, E. et al. De novo design of a non-local β-sheet protein with high stability and accuracy. Nat. Struct. Mol. Biol. 25, 1028–1034 (2018).",{"doi":5503},"10.1038\u002Fs41594-018-0141-6",{"id":24,"text":5505,"url":24,"identifiers":5506},"Murphy, G. S. et al. Computational de novo design of a four-helix bundle protein–DND_4HB. Protein Sci. 24, 434–445 (2015).",{"doi":5507},"10.1002\u002Fpro.2577",{"id":24,"text":5509,"url":24,"identifiers":5510},"Jacobs, T. M. et al. Design of structurally distinct proteins using strategies inspired by evolution. Science 352, 687–690 (2016).",{"doi":5511},"10.1126\u002Fscience.aad8036",{"id":24,"text":5513,"url":24,"identifiers":5514},"Guffy, S. L., Teets, F. D., Langlois, M. I. & Kuhlman, B. Protocols for requirement-driven protein design in the Rosetta modeling program. J. Chem. Inf. Model. 58, 895–901 (2018).",{"doi":5515},"10.1021\u002Facs.jcim.8b00060",{"id":24,"text":5517,"url":24,"identifiers":5518},"Lin, Y.-R. et al. Control over overall shape and size in de novo designed proteins. Proc. Natl Acad. Sci. USA 112, E5478–85 (2015).",{"doi":5519},"10.1073\u002Fpnas.1509508112",{"id":24,"text":5521,"url":24,"identifiers":5522},"Koga, N. et al. Principles for designing ideal protein structures. Nature 491, 222–227 (2012).",{"doi":5523},"10.1038\u002Fnature11600",{"id":24,"text":5525,"url":24,"identifiers":5526},"Crick, F. H. C. The Fourier transform of a coiled-coil. Acta Crystallogr. 6, 685–689 (1953).",{"doi":5527},"10.1107\u002FS0365110X53001952",{"id":24,"text":5529,"url":24,"identifiers":5530},"Huang, P.-S. et al. High thermodynamic stability of parametrically designed helical bundles. Science 346, 481–485 (2014).",{"doi":5531},"10.1126\u002Fscience.1257481",{"id":24,"text":5533,"url":24,"identifiers":5534},"Lu, P. et al. Accurate computational design of multipass transmembrane proteins. Science 359, 1042–1046 (2018).",{"doi":5535},"10.1126\u002Fscience.aaq1739",{"id":24,"text":5537,"url":24,"identifiers":5538},"Thomson, A. R. et al. Computational design of water-soluble α-helical barrels. Science 346, 485–488 (2014).",{"doi":5539},"10.1126\u002Fscience.1257452",{"id":24,"text":5541,"url":24,"identifiers":5542},"Tinberg, C. E. et al. Computational design of ligand-binding proteins with high affinity and selectivity. Nature 501, 212–216 (2013).",{"doi":5543},"10.1038\u002Fnature12443",{"id":24,"text":5545,"url":24,"identifiers":5546},"Röthlisberger, D. et al. Kemp elimination catalysts by computational enzyme design. Nature 453, 190–195 (2008).",{"doi":5547},"10.1038\u002Fnature06879",{"id":24,"text":5549,"url":24,"identifiers":5550},"Alford, R. F. et al. The Rosetta all-atom energy function for macromolecular modeling and design. J. Chem. Theory Comput. 13, 3031–3048 (2017).",{"doi":5551},"10.1021\u002Facs.jctc.7b00125",{"id":24,"text":5553,"url":24,"identifiers":5554},"Boas, F. E. & Harbury, P. B. Potential energy functions for protein design. Curr. Opin. Struct. Biol. 17, 199–204 (2007).",{"doi":5555},"10.1016\u002Fj.sbi.2007.03.006",{"id":24,"text":5557,"url":24,"identifiers":5558},"O’Meara, M. J. et al. Combined covalent-electrostatic model of hydrogen bonding improves structure prediction with Rosetta. J. Chem. Theory Comput. 11, 609–622 (2015).",{"doi":5559},"10.1021\u002Fct500864r",{"id":24,"text":5561,"url":24,"identifiers":5562},"Gainza, P., Nisonoff, H. M. & Donald, B. R. Algorithms for protein design. Curr. Opin. Struct. Biol. 39, 16–26 (2016).",{"doi":5563},"10.1016\u002Fj.sbi.2016.03.006",{"id":24,"text":5565,"url":24,"identifiers":5566},"Dunbrack, R. L. Jr Rotamer libraries in the 21st century. Curr. Opin. Struct. Biol. 12, 431–440 (2002).",{"doi":5567},"10.1016\u002FS0959-440X(02)00344-5",{"id":24,"text":5569,"url":24,"identifiers":5570},"Kuhlman, B. & Baker, D. Native protein sequences are close to optimal for their structures. Proc. Natl Acad. Sci. USA 97, 10383–10388 (2000).",{"doi":5571},"10.1073\u002Fpnas.97.19.10383",{"id":24,"text":5573,"url":24,"identifiers":5574},"Traoré, S. et al. Fast search algorithms for computational protein design. J. Comput. Chem. 37, 1048–1058 (2016).",{"doi":5575},"10.1002\u002Fjcc.24290",{"id":24,"text":5577,"url":24,"identifiers":5578},"Hallen, M. A. et al. OSPREY 3.0: open-source protein redesign for you, with powerful new features. J. Comput. Chem. 39, 2494–2507 (2018).",{"doi":5579},"10.1002\u002Fjcc.25522",{"id":24,"text":5581,"url":24,"identifiers":5582},"Lapidoth, G. et al. Highly active enzymes by automated combinatorial backbone assembly and sequence design. Nat. Commun. 9, 2780 (2018).",{"doi":5583},"10.1038\u002Fs41467-018-05205-5",{"id":24,"text":5585,"url":24,"identifiers":5586},"Ollikainen, N., de Jong, R. M. & Kortemme, T. Coupling protein side-chain and backbone flexibility improves the re-design of protein-ligand specificity. PLoS Comput. Biol. 11, e1004335 (2015).",{"doi":5587},"10.1371\u002Fjournal.pcbi.1004335",{"id":24,"text":5589,"url":24,"identifiers":5590},"Hallen, M. A. & Donald, B. R. CATS (coordinates of atoms by taylor series): protein design with backbone flexibility in all locally feasible directions. Bioinformatics 33, i5–i12 (2017).",{"doi":5591},"10.1093\u002Fbioinformatics\u002Fbtx277",{"id":24,"text":5593,"url":24,"identifiers":5594},"Mackenzie, C. O., Zhou, J. & Grigoryan, G. Tertiary alphabet for the observable protein structural universe. Proc. Natl Acad. Sci. USA 113, E7438–E7447 (2016).",{"doi":5595},"10.1073\u002Fpnas.1607178113",{"id":24,"text":5597,"url":24,"identifiers":5598},"Frappier, V., Jenson, J. M., Zhou, J., Grigoryan, G. & Keating, A. E. Tertiary structural motif sequence statistics enable facile prediction and design of peptides that bind anti-apoptotic Bfl-1 and Mcl-1. Structure 27, 606–617 (2019). Instead of using an all-atom model of the complex to calculate interaction energies, Frappier et al. employed a knowledge-based approach with sequence preferences from structural motifs similar to the designed interface to predict binding energies.",{"doi":5599},"10.1016\u002Fj.str.2019.01.008",{"id":24,"text":5601,"url":24,"identifiers":5602},"Boyken, S. E. et al. De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity. Science 352, 680–687 (2016).",{"doi":5603},"10.1126\u002Fscience.aad8865",{"id":24,"text":5605,"url":24,"identifiers":5606},"Chen, Z. et al. Programmable design of orthogonal protein heterodimers. Nature 565, 106–111 (2019).",{"doi":5607},"10.1038\u002Fs41586-018-0802-y",{"id":24,"text":5609,"url":24,"identifiers":5610},"Maguire, J. B., Boyken, S. E., Baker, D. & Kuhlman, B. Rapid sampling of hydrogen bond networks for computational protein design. J. Chem. Theory Comput. 14, 2751–2760 (2018).",{"doi":5611},"10.1021\u002Facs.jctc.8b00033",{"id":24,"text":5613,"url":24,"identifiers":5614},"Harbury, P. B., Plecs, J. J., Tidor, B., Alber, T. & Kim, P. S. High-resolution protein design with backbone freedom. Science 282, 1462–1467 (1998).",{"doi":5615},"10.1126\u002Fscience.282.5393.1462",{"id":24,"text":5617,"url":24,"identifiers":5618},"Leaver-Fay, A., Jacak, R., Stranges, P. B. & Kuhlman, B. A generic program for multistate protein design. PLoS ONE 6, e20937 (2011).",{"doi":5619},"10.1371\u002Fjournal.pone.0020937",{"id":24,"text":5621,"url":24,"identifiers":5622},"Negron, C. & Keating, A. E. Multistate protein design using CLEVER and CLASSY. Methods Enzymol. 523, 171–190 (2013).",{"doi":5623},"10.1016\u002FB978-0-12-394292-0.00008-4",{"id":24,"text":5625,"url":24,"identifiers":5626},"Allen, B. D. & Mayo, S. L. An efficient algorithm for multistate protein design based on FASTER. J. Comput. Chem. 31, 904–916 (2010).",{"doi":5627},"10.1002\u002Fjcc.21375",{"id":24,"text":5629,"url":24,"identifiers":5630},"Löffler, P., Schmitz, S., Hupfeld, E., Sterner, R. & Merkl, R. Rosetta:MSF: a modular framework for multi-state computational protein design. PLoS Comput. Biol. 13, e1005600 (2017).",{},{"id":24,"text":5632,"url":24,"identifiers":5633},"Goldenzweig, A. et al. Automated structure- and sequence-based design of proteins for high bacterial expression and stability. Mol. Cell 63, 337–346 (2016). This study uses protein design simulations coupled with sequence conservation information to create an effective protocol for identifying sets of mutations that increase protein thermostability and expression.",{"doi":5634},"10.1016\u002Fj.molcel.2016.06.012",{"id":24,"text":5636,"url":24,"identifiers":5637},"Rocklin, G. J. et al. Global analysis of protein folding using massively parallel design, synthesis, and testing. Science 357, 168–175 (2017).",{"doi":5638},"10.1126\u002Fscience.aan0693",{"id":24,"text":5640,"url":24,"identifiers":5641},"Gainza-Cirauqui, P. & Correia, B. E. Computational protein design — the next generation tool to expand synthetic biology applications. Curr. Opin. Biotechnol. 52, 145–152 (2018).",{"doi":5642},"10.1016\u002Fj.copbio.2018.04.001",{"id":24,"text":5644,"url":24,"identifiers":5645},"Wrenbeck, E. E., Faber, M. S. & Whitehead, T. A. Deep sequencing methods for protein engineering and design. Curr. Opin. Struct. Biol. 45, 36–44 (2017).",{"doi":5646},"10.1016\u002Fj.sbi.2016.11.001",{"id":24,"text":5648,"url":24,"identifiers":5649},"Malakauskas, S. M. & Mayo, S. L. Design, structure and stability of a hyperthermophilic protein variant. Nat. Struct. Biol. 5, 470–475 (1998).",{"doi":5650},"10.1038\u002Fnsb0698-470",{"id":24,"text":5652,"url":24,"identifiers":5653},"Magliery, T. J. Protein stability: computation, sequence statistics, and new experimental methods. Curr. Opin. Struct. Biol. 33, 161–168 (2015).",{"doi":5654},"10.1016\u002Fj.sbi.2015.09.002",{"id":24,"text":5656,"url":24,"identifiers":5657},"Goldenzweig, A. & Fleishman, S. J. Principles of protein stability and their application in computational design. Annu. Rev. Biochem. 87, 105–129 (2018).",{"doi":5658},"10.1146\u002Fannurev-biochem-062917-012102",{"id":24,"text":5660,"url":24,"identifiers":5661},"Borgo, B. & Havranek, J. J. Automated selection of stabilizing mutations in designed and natural proteins. Proc. Natl Acad. Sci. USA 109, 1494–1499 (2012).",{"doi":5662},"10.1073\u002Fpnas.1115172109",{"id":24,"text":5664,"url":24,"identifiers":5665},"Dantas, G., Kuhlman, B., Callender, D., Wong, M. & Baker, D. A large scale test of computational protein design: folding and stability of nine completely redesigned globular proteins. J. Mol. Biol. 332, 449–460 (2003).",{"doi":5666},"10.1016\u002FS0022-2836(03)00888-X",{"id":24,"text":5668,"url":24,"identifiers":5669},"Murphy, G. S. et al. Increasing sequence diversity with flexible backbone protein design: the complete redesign of a protein hydrophobic core. Structure 20, 1086–1096 (2012).",{"doi":5670},"10.1016\u002Fj.str.2012.03.026",{"id":24,"text":5672,"url":24,"identifiers":5673},"Bednar, D. et al. FireProt: energy- and evolution-based computational design of thermostable multiple-point mutants. PLoS Comput. Biol. 11, e1004556 (2015).",{"doi":5674},"10.1371\u002Fjournal.pcbi.1004556",{"id":24,"text":5676,"url":24,"identifiers":5677},"Lehmann, M., Pasamontes, L., Lassen, S. F. & Wyss, M. The consensus concept for thermostability engineering of proteins. Biochim. Biophys. Acta 1543, 408–415 (2000).",{"doi":5678},"10.1016\u002FS0167-4838(00)00238-7",{"id":24,"text":5680,"url":24,"identifiers":5681},"Campeotto, I. et al. One-step design of a stable variant of the malaria invasion protein RH5 for use as a vaccine immunogen. Proc. Natl Acad. Sci. USA 114, 998–1002 (2017).",{"doi":5682},"10.1073\u002Fpnas.1616903114",{"id":24,"text":5684,"url":24,"identifiers":5685},"Kapp, G. T. et al. Control of protein signaling using a computationally designed GTPase\u002FGEF orthogonal pair. Proc. Natl Acad. Sci. USA 109, 5277–5282 (2012).",{"doi":5686},"10.1073\u002Fpnas.1114487109",{"id":24,"text":5688,"url":24,"identifiers":5689},"Jenson, J. M., Ryan, J. A., Grant, R. A., Letai, A. & Keating, A. E. Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1. eLife 6, e25541 (2017).",{"doi":5690},"10.7554\u002FeLife.25541",{"id":24,"text":5692,"url":24,"identifiers":5693},"Froning, K. J. et al. Computational design of a specific heavy chain\u002Fκ light chain interface for expressing fully IgG bispecific antibodies. Protein Sci. 26, 2021–2038 (2017).",{"doi":5694},"10.1002\u002Fpro.3240",{"id":24,"text":5696,"url":24,"identifiers":5697},"Leaver-Fay, A. et al. Computationally designed bispecific antibodies using negative state repertoires. Structure 24, 641–651 (2016).",{"doi":5698},"10.1016\u002Fj.str.2016.02.013",{"id":24,"text":5700,"url":24,"identifiers":5701},"Lewis, S. M. et al. Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface. Nat. Biotechnol. 32, 191–198 (2014). In this study, multi-state design simulations are used to create altered specificity interactions between antibody constant domains, allowing the proper assembly of IgG antibodies that recognize two separate antigens simultaneously.",{"doi":5702},"10.1038\u002Fnbt.2797",{"id":24,"text":5704,"url":24,"identifiers":5705},"Krishnamurthy, A. & Jimeno, A. Bispecific antibodies for cancer therapy: a review. Pharmacol. Ther. 185, 122–134 (2018).",{"doi":5706},"10.1016\u002Fj.pharmthera.2017.12.002",{"id":24,"text":5708,"url":24,"identifiers":5709},"Berger, S. et al. Computationally designed high specificity inhibitors delineate the roles of BCL2 family proteins in cancer. eLife 5, e20352 (2016).",{"doi":5710},"10.7554\u002FeLife.20352",{"id":24,"text":5712,"url":24,"identifiers":5713},"Stranges, P. B. & Kuhlman, B. A comparison of successful and failed protein interface designs highlights the challenges of designing buried hydrogen bonds. Protein Sci. 22, 74–82 (2013).",{"doi":5714},"10.1002\u002Fpro.2187",{"id":24,"text":5716,"url":24,"identifiers":5717},"King, N. P. et al. Computational design of self-assembling protein nanomaterials with atomic level accuracy. Science 336, 1171–1174 (2012).",{"doi":5718},"10.1126\u002Fscience.1219364",{"id":24,"text":5720,"url":24,"identifiers":5721},"King, N. P. et al. Accurate design of co-assembling multi-component protein nanomaterials. Nature 510, 103–108 (2014).",{"doi":5722},"10.1038\u002Fnature13404",{"id":24,"text":5724,"url":24,"identifiers":5725},"Bale, J. B. et al. Accurate design of megadalton-scale two-component icosahedral protein complexes. Science 353, 389–394 (2016). One of several papers in which this team demonstrate that protein interface design combined with modelling of higher-order symmetries can be used to create large, multi-component protein cages.",{"doi":5726},"10.1126\u002Fscience.aaf8818",{"id":24,"text":5728,"url":24,"identifiers":5729},"Butterfield, G. L. et al. Evolution of a designed protein assembly encapsulating its own RNA genome. Nature 552, 415–420 (2017).",{"doi":5730},"10.1038\u002Fnature25157",{"id":24,"text":5732,"url":24,"identifiers":5733},"Liu, Y., Gonen, S., Gonen, T. & Yeates, T. O. Near-atomic cryo-EM imaging of a small protein displayed on a designed scaffolding system. Proc. Natl Acad. Sci. USA 115, 3362–3367 (2018).",{"doi":5734},"10.1073\u002Fpnas.1718825115",{"id":24,"text":5736,"url":24,"identifiers":5737},"Liu, Y., Huynh, D. T. & Yeates, T. O. A 3.8 Å resolution cryo-EM structure of a small protein bound to an imaging scaffold. Nat. Commun. 10, 1864 (2019).",{"doi":5738},"10.1038\u002Fs41467-019-09836-0",{"id":24,"text":5740,"url":24,"identifiers":5741},"Marcandalli, J. et al. Induction of potent neutralizing antibody responses by a designed protein nanoparticle vaccine for respiratory syncytial virus. Cell 176, 1420–1431 (2019).",{"doi":5742},"10.1016\u002Fj.cell.2019.01.046",{"id":24,"text":5744,"url":24,"identifiers":5745},"LjubetiČ, A. et al. Design of coiled-coil protein-origami cages that self-assemble in vitro and in vivo. Nat. Biotechnol. 35, 1094–1101 (2017).",{"doi":5746},"10.1038\u002Fnbt.3994",{"id":24,"text":5748,"url":24,"identifiers":5749},"Lai, Y.-T., Cascio, D. & Yeates, T. O. Structure of a 16-nm cage designed by using protein oligomers. Science 336, 1129 (2012).",{"doi":5750},"10.1126\u002Fscience.1219351",{"id":24,"text":5752,"url":24,"identifiers":5753},"Shen, H. et al. De novo design of self-assembling helical protein filaments. Science 362, 705–709 (2018).",{"doi":5754},"10.1126\u002Fscience.aau3775",{"id":24,"text":5756,"url":24,"identifiers":5757},"Gonen, S., DiMaio, F., Gonen, T. & Baker, D. Design of ordered two-dimensional arrays mediated by noncovalent protein-protein interfaces. Science 348, 1365–1368 (2015).",{"doi":5758},"10.1126\u002Fscience.aaa9897",{"id":24,"text":5760,"url":24,"identifiers":5761},"Zhang, H. V. et al. Computationally designed peptides for self-assembly of nanostructured lattices. Sci. Adv. 2, e1600307 (2016).",{"doi":5762},"10.1126\u002Fsciadv.1600307",{"id":24,"text":5764,"url":24,"identifiers":5765},"Tian, Y. et al. Nanotubes, plates, and needles: pathway-dependent self-assembly of computationally designed peptides. Biomacromolecules 19, 4286–4298 (2018).",{"doi":5766},"10.1021\u002Facs.biomac.8b01163",{"id":24,"text":5768,"url":24,"identifiers":5769},"Fleishman, S. J. et al. Computational design of proteins targeting the conserved stem region of influenza hemagglutinin. Science 332, 816–821 (2011).",{"doi":5770},"10.1126\u002Fscience.1202617",{"id":24,"text":5772,"url":24,"identifiers":5773},"Chevalier, A. et al. Massively parallel de novo protein design for targeted therapeutics. Nature 550, 74–79 (2017).",{"doi":5774},"10.1038\u002Fnature23912",{"id":24,"text":5776,"url":24,"identifiers":5777},"Adolf-Bryfogle, J. et al. RosettaAntibodyDesign (RAbD): a general framework for computational antibody design. PLoS Comput. Biol. 14, e1006112 (2018).",{"doi":5778},"10.1371\u002Fjournal.pcbi.1006112",{"id":24,"text":5780,"url":24,"identifiers":5781},"Kundert, K. & Kortemme, T. Computational design of structured loops for new protein functions. Biol. Chem. 400, 275–288 (2019).",{"doi":5782},"10.1515\u002Fhsz-2018-0348",{"id":24,"text":5784,"url":24,"identifiers":5785},"Adolf-Bryfogle, J., Xu, Q., North, B., Lehmann, A. & Dunbrack, R. L. Jr PyIgClassify: a database of antibody CDR structural classifications. Nucleic Acids Res. 43, D432–D438 (2015).",{"doi":5786},"10.1093\u002Fnar\u002Fgku1106",{"id":24,"text":5788,"url":24,"identifiers":5789},"Baran, D. et al. Principles for computational design of binding antibodies. Proc. Natl Acad. Sci. USA 114, 10900–10905 (2017).",{"doi":5790},"10.1073\u002Fpnas.1707171114",{"id":24,"text":5792,"url":24,"identifiers":5793},"Kulp, D. W. & Schief, W. R. Advances in structure-based vaccine design. Curr. Opin. Virol. 3, 322–331 (2013).",{"doi":5794},"10.1016\u002Fj.coviro.2013.05.010",{"id":24,"text":5796,"url":24,"identifiers":5797},"Salvat, R. S. et al. Computationally optimized deimmunization libraries yield highly mutated enzymes with low immunogenicity and enhanced activity. Proc. Natl Acad. Sci. USA 114, E5085–E5093 (2017).",{"doi":5798},"10.1073\u002Fpnas.1621233114",{"id":24,"text":5800,"url":24,"identifiers":5801},"Bick, M. J. et al. Computational design of environmental sensors for the potent opioid fentanyl. eLife 6, e28909 (2017).",{"doi":5802},"10.7554\u002FeLife.28909",{"id":24,"text":5804,"url":24,"identifiers":5805},"Polizzi, N. F. et al. De novo design of a hyperstable non-natural protein-ligand complex with sub-Å accuracy. Nat. Chem. 9, 1157–1164 (2017).",{"doi":5806},"10.1038\u002Fnchem.2846",{"id":24,"text":5808,"url":24,"identifiers":5809},"Reeve, S. M. et al. Protein design algorithms predict viable resistance to an experimental antifolate. Proc. Natl Acad. Sci. USA 112, 749–754 (2015).",{"doi":5810},"10.1073\u002Fpnas.1411548112",{"id":24,"text":5812,"url":24,"identifiers":5813},"Kiss, G., Çelebi-Ölçüm, N., Moretti, R., Baker, D. & Houk, K. N. Computational enzyme design. Angew. Chem. Int. Ed. Engl. 52, 5700–5725 (2013).",{"doi":5814},"10.1002\u002Fanie.201204077",{"id":24,"text":5816,"url":24,"identifiers":5817},"Baker, D. An exciting but challenging road ahead for computational enzyme design. Protein Sci. 19, 1817–1819 (2010).",{"doi":5818},"10.1002\u002Fpro.481",{"id":24,"text":5820,"url":24,"identifiers":5821},"Ambroggio, X. I. & Kuhlman, B. Computational design of a single amino acid sequence that can switch between two distinct protein folds. J. Am. Chem. Soc. 128, 1154–1161 (2006).",{"doi":5822},"10.1021\u002Fja054718w",{"id":24,"text":5824,"url":24,"identifiers":5825},"Joh, N. H. et al. De novo design of a transmembrane Zn2+-transporting four-helix bundle. Science 346, 1520–1524 (2014).",{"doi":5826},"10.1126\u002Fscience.1261172",{"id":24,"text":5828,"url":24,"identifiers":5829},"Davey, J. A., Damry, A. M., Goto, N. K. & Chica, R. A. Rational design of proteins that exchange on functional timescales. Nat. Chem. Biol. 13, 1280–1285 (2017).",{"doi":5830},"10.1038\u002Fnchembio.2503",{"id":24,"text":5832,"url":24,"identifiers":5833},"Guntas, G. et al. Engineering an improved light-induced dimer (iLID) for controlling the localization and activity of signaling proteins. Proc. Natl Acad. Sci. USA 112, 112–117 (2015).",{"doi":5834},"10.1073\u002Fpnas.1417910112",{"id":24,"text":5836,"url":24,"identifiers":5837},"Dagliyan, O. et al. Engineering extrinsic disorder to control protein activity in living cells. Science 354, 1441–1444 (2016).",{"doi":5838},"10.1126\u002Fscience.aah3404",{"id":24,"text":5840,"url":24,"identifiers":5841},"Dagliyan, O. et al. Computational design of chemogenetic and optogenetic split proteins. Nat. Commun. 9, 4042 (2018).",{"doi":5842},"10.1038\u002Fs41467-018-06531-4",{"id":24,"text":5844,"url":24,"identifiers":5845},"Blacklock, K. M., Yachnin, B. J., Woolley, G. A. & Khare, S. D. Computational design of a photocontrolled cytosine deaminase. J. Am. Chem. Soc. 140, 14–17 (2017).",{"doi":5846},"10.1021\u002Fjacs.7b08709",{"id":24,"text":5848,"url":24,"identifiers":5849},"Hoersch, D., Roh, S.-H., Chiu, W. & Kortemme, T. Reprogramming an ATP-driven protein machine into a light-gated nanocage. Nat. Nanotechnol. 8, 928–932 (2013).",{"doi":5850},"10.1038\u002Fnnano.2013.242",{"id":24,"text":5852,"url":24,"identifiers":5853},"Lindorff-Larsen, K., Piana, S., Dror, R. O. & Shaw, D. E. How fast-folding proteins fold. Science 334, 517–520 (2011).",{"doi":5854},"10.1126\u002Fscience.1208351",{"id":24,"text":5856,"url":24,"identifiers":5857},"Dror, R. O. et al. Structural basis for nucleotide exchange in heterotrimeric G proteins. Science 348, 1361–1365 (2015).",{"doi":5858},"10.1126\u002Fscience.aaa5264",{"id":24,"text":5860,"url":24,"identifiers":5861},"Correia, B. E. et al. Proof of principle for epitope-focused vaccine design. Nature 507, 201–206 (2014). Correia et al. used a de novo protein design to generate a small protein that mimics a conformational epitope from RSV and elicits neutralizing antibodies in animal studies.",{"doi":5862},"10.1038\u002Fnature12966",{"id":5864,"createTime":5865,"updateTime":5865,"relativeEntities":5866,"slug":5867,"properties":5868,"entityType":131,"verifyStatus":132,"verifyTime":5865,"verifyNote":133,"languages":5879,"translateLanguages":24,"viewCount":25,"primaryUrl":5880,"fullTextUrl":24,"authors":5881,"publicationType":174,"publisherRelationship":5901,"citationCount":5954,"citationInfo":5955,"publishDate":1797,"publishYear":1794,"citationAnalyzeStatus":23,"lastCitationAnalyze":24,"indexDatabases":5969,"openAccess":24,"references":5970,"isForceReanalyzing":409},"2d658141-d14e-4aee-9675-da41a08ec989","2025-02-05T17:45:01.753+00:00",[],"Mitochondrial-fusion-and-fission-in-cell-life-and-death",{"openalex":5869,"mag":5871,"title":5873,"pm":5875,"doi":5877},{"VOID":5870},"W2032234589",{"VOID":5872},"2032234589",{"EN":5874},"Mitochondrial fusion and fission in cell life and death",{"VOID":5876},"21102612",{"VOID":5878},"10.1038\u002Fnrm3013",[135],"https:\u002F\u002Fwww.nature.com\u002Farticles\u002Fnrm3013",[5882],{"id":5883,"sortIndex":25,"researcher":24,"roles":5884,"affiliations":5885,"properties":5894,"displayName":5898,"givenName":24,"familyName":24},"06c8fc0e-e5ac-4386-b3be-f86e7ef8c0b1",[],[5886],{"id":5887,"sortIndex":25,"affiliation":5888,"properties":24},"81cd706b-be3b-4fd2-85ec-bc28241a6da5",{"id":5887,"createTime":24,"updateTime":24,"relativeEntities":5889,"slug":24,"properties":5890,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":5893,"statistic":24},[],{"title":5891},{"VI":5892},"Institut für Zellbiologie, Universität Bayreuth, 95440 Bayreuth, Germany",[],{"orcid":5895,"title":5897,"openalex":5899},{"VOID":5896},"https:\u002F\u002Forcid.org\u002F0000-0002-2991-1604",{"EN":5898},"Benedikt Westermann",{"VOID":5900},"A5003964137",{"url":24,"publisher":5902,"properties":5949},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":5903,"slug":10,"properties":5904,"entityType":22,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":25,"subjectFields":5909,"manageAffiliations":5918,"indexDatabases":5929,"url":90,"thumbnailPath":24,"statistic":5944,"gsStatistic":24,"type":24,"analyzePriority":24},[],{"country":5905,"eissn":5906,"issn":5907,"title":5908},{"VOID":13},{"VOID":15},{"VOID":17},{"EN":19},[5910,5914],{"id":28,"createTime":24,"updateTime":24,"relativeEntities":5911,"label":5912,"description":5913,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":31},{},{"id":34,"createTime":24,"updateTime":24,"relativeEntities":5915,"label":5916,"description":5917,"parentId":24,"standard":24,"scholarHubFieldId":24},[],{"EN":37},{},[5919,5924],{"id":41,"createTime":24,"updateTime":24,"relativeEntities":5920,"slug":24,"properties":5921,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":5923,"statistic":24},[],{"title":5922},{"EN":45},[],{"id":48,"createTime":24,"updateTime":24,"relativeEntities":5925,"slug":24,"properties":5926,"entityType":24,"verifyStatus":24,"verifyTime":24,"verifyNote":24,"languages":24,"translateLanguages":24,"viewCount":24,"url":24,"parentIds":5928,"statistic":24},[],{"title":5927},{"EN":52},[],[5930,5937],{"id":56,"indexDatabase":5931,"url":69,"indexYears":24,"academicFieldIds":5936,"indexDatabaseRanking":24},{"id":58,"createTime":24,"updateTime":24,"relativeEntities":5932,"label":5933,"description":5934,"key":65,"publicationTags":5935,"standard":24},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":5938,"url":84,"indexYears":85,"academicFieldIds":5943,"indexDatabaseRanking":89},{"id":75,"createTime":24,"updateTime":24,"relativeEntities":5939,"label":5940,"description":5941,"key":81,"publicationTags":5942,"standard":24},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88],{"impactFactor":25,"impactFactorByYear":5945,"i10Index":97,"i10IndexLast5Year":25,"totalPublication":97,"totalPublicationByYear":5946,"totalCitation":100,"totalCitationByYear":5947,"totalCitationPerPublication":106,"totalCitationPerPublicationByYear":5948,"hindexLast5Year":97,"hindex":97},{"2016":93,"2017":94,"2019":95,"2020":96},{"2007":99,"2009":99,"2015":99,"2018":99},{"2007":102,"2009":103,"2015":104,"2018":105},{"2007":102,"2009":103,"2015":104,"2018":105},{"issue":5950,"pages":5951,"volume":5953},{"VOID":1787},{"VOID":5952},"872-884",{"VOID":1791},1798,{"total":5954,"publishYear":1794,"statisticByYear":5956},{"2012":5957,"2013":5958,"2014":5959,"2015":5960,"2016":5961,"2017":5962,"2018":5963,"2019":5964,"2020":5965,"2021":5966,"2022":2151,"2023":5967,"2024":5968},121,97,109,119,113,143,117,124,186,189,130,150,[67,89],[5971,5975,5979,5983,5987,5991,5995,5999,6003,6007,6011,6015,6019,6023,6027,6031,6035,6039,6043,6047,6051,6055,6059,6063,6067,6071,6075,6079,6083,6087,6091,6095,6099,6103,6107,6111,6115,6119,6123,6127,6131,6135,6139,6143,6147,6151,6155,6159,6163,6167,6171,6175,6179,6183,6187,6191,6195,6199,6203,6207,6211,6215,6219,6223,6227,6231,6235,6239,6243,6247,6251,6255,6259,6263,6267,6271,6275,6279,6283,6287,6291,6295,6299,6303,6307,6311,6315,6319,6323,6327,6331,6335,6339,6343,6347,6351,6355,6359,6363,6367,6371,6375,6379,6383,6387,6391,6395,6399,6403,6407,6411,6415,6419,6423,6427,6431,6435,6439,6443,6447,6451,6455,6459,6463,6467,6471,6475,6479,6483,6487,6491,6495,6499,6503],{"id":24,"text":5972,"url":24,"identifiers":5973},"Palade, G. E. An electron microscope study of the mitochondrial structure. J. Histochem. Cytochem. 1, 188–211 (1953).",{"doi":5974},"10.1177\u002F1.4.188",{"id":24,"text":5976,"url":24,"identifiers":5977},"Bereiter-Hahn, J. Behavior of mitochondria in the living cell. Int. Rev. Cytol. 122, 1–63 (1990).",{"doi":5978},"10.1016\u002FS0074-7696(08)61205-X",{"id":24,"text":5980,"url":24,"identifiers":5981},"Skulachev, V. P. Mitochondrial filaments and clusters as intracellular power-transmitting cables. Trends Biochem. Sci. 26, 23–29 (2001).",{"doi":5982},"10.1016\u002FS0968-0004(00)01735-7",{"id":24,"text":5984,"url":24,"identifiers":5985},"Collins, T. J., Berridge, M. J., Lipp, P. & Bootman, M. D. Mitochondria are morphologically and functionally heterogeneous within cells. EMBO J. 21, 1616–1627 (2002).",{"doi":5986},"10.1093\u002Femboj\u002F21.7.1616",{"id":24,"text":5988,"url":24,"identifiers":5989},"Detmer, S. A. & Chan, D. C. Functions and dysfunctions of mitochondrial dynamics. Nature Rev. Mol. Cell Biol. 8, 870–879 (2007).",{"doi":5990},"10.1038\u002Fnrm2275",{"id":24,"text":5992,"url":24,"identifiers":5993},"Hoppins, S., Lackner, L. & Nunnari, J. The machines that divide and fuse mitochondria. Annu. Rev. Biochem. 76, 751–780 (2007).",{"doi":5994},"10.1146\u002Fannurev.biochem.76.071905.090048",{"id":24,"text":5996,"url":24,"identifiers":5997},"Okamoto, K. & Shaw, J. M. Mitochondrial morphology and dynamics in yeast and multicellular eukaryotes. Annu. Rev. Genet. 39, 503–536 (2005).",{"doi":5998},"10.1146\u002Fannurev.genet.38.072902.093019",{"id":24,"text":6000,"url":24,"identifiers":6001},"Martens, S. & McMahon, H. T. Mechanisms of membrane fusion: disparate players and common principles. Nature Rev. Mol. Cell Biol. 9, 543–556 (2008).",{"doi":6002},"10.1038\u002Fnrm2417",{"id":24,"text":6004,"url":24,"identifiers":6005},"Hales, K. G. & Fuller, M. T. Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase. Cell 90, 121–129 (1997). Reports the identification of the first known mediator of mitochondrial fusion and, at the same time, describes the role of fusion in remodelling of mitochondria during spermatogenesis.",{"doi":6006},"10.1016\u002FS0092-8674(00)80319-0",{"id":24,"text":6008,"url":24,"identifiers":6009},"Rapaport, D., Brunner, M., Neupert, W. & Westermann, B. Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae. J. Biol. Chem. 273, 20150–20155 (1998).",{"doi":6010},"10.1074\u002Fjbc.273.32.20150",{"id":24,"text":6012,"url":24,"identifiers":6013},"Hermann, G. J. et al. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p. J. Cell Biol. 143, 359–373 (1998).",{"doi":6014},"10.1083\u002Fjcb.143.2.359",{"id":24,"text":6016,"url":24,"identifiers":6017},"Kanazawa, T. et al. The C. elegans Opa1 homologue EAT-3 is essential for resistance to free radicals. PLoS Genet. 4, e1000022 (2008).",{"doi":6018},"10.1371\u002Fjournal.pgen.1000022",{"id":24,"text":6020,"url":24,"identifiers":6021},"Santel, A. & Fuller, M. T. Control of mitochondrial morphology by a human mitofusin. J. Cell Sci. 114, 867–874 (2001).",{"doi":6022},"10.1242\u002Fjcs.114.5.867",{"id":24,"text":6024,"url":24,"identifiers":6025},"Fritz, S., Rapaport, D., Klanner, E., Neupert, W. & Westermann, B. Connection of the mitochondrial outer and inner membranes by Fzo1 is critical for organellar fusion. J. Cell Biol. 152, 683–692 (2001).",{"doi":6026},"10.1083\u002Fjcb.152.4.683",{"id":24,"text":6028,"url":24,"identifiers":6029},"Rojo, M., Legros, F., Chateau, D. & Lombes, A. Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J. Cell Sci. 115, 1663–1674 (2002).",{"doi":6030},"10.1242\u002Fjcs.115.8.1663",{"id":24,"text":6032,"url":24,"identifiers":6033},"Meeusen, S. et al. Mitochondrial inner-membrane fusion and crista maintenance requires the dynamin-related GTPase Mgm1. Cell 127, 383–395 (2006).",{"doi":6034},"10.1016\u002Fj.cell.2006.09.021",{"id":24,"text":6036,"url":24,"identifiers":6037},"Herlan, M., Vogel, F., Bornhövd, C., Neupert, W. & Reichert, A. S. Processing of Mgm1 by the rhomboid-type protease Pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial DNA. J. Biol. Chem. 278, 27781–27788 (2003).",{"doi":6038},"10.1074\u002Fjbc.M211311200",{"id":24,"text":6040,"url":24,"identifiers":6041},"McQuibban, G. A., Saurya, S. & Freeman, M. Mitochondrial membrane remodelling regulated by a conserved rhomboid protease. Nature 423, 537–541 (2003).",{"doi":6042},"10.1038\u002Fnature01633",{"id":24,"text":6044,"url":24,"identifiers":6045},"Cipolat, S., Martins de Brito, O., Dal Zilio, B. & Scorrano, L. OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc. Natl Acad. Sci. USA 101, 15927–15932 (2004).",{"doi":6046},"10.1073\u002Fpnas.0407043101",{"id":24,"text":6048,"url":24,"identifiers":6049},"Yarosh, W. et al. The molecular mechanisms of OPA1-mediated optic atrophy in Drosophila model and prospects for antioxidant treatment. PLoS Genet. 4, e6 (2008).",{"doi":6050},"10.1371\u002Fjournal.pgen.0040006",{"id":24,"text":6052,"url":24,"identifiers":6053},"Cipolat, S. et al. Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. Cell 126, 163–175 (2006).",{"doi":6054},"10.1016\u002Fj.cell.2006.06.021",{"id":24,"text":6056,"url":24,"identifiers":6057},"Griparic, L., Kanazawa, T. & van der Bliek, A. M. Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage. J. Cell Biol. 178, 757–764 (2007).",{"doi":6058},"10.1083\u002Fjcb.200704112",{"id":24,"text":6060,"url":24,"identifiers":6061},"Ishihara, N., Fujita, Y., Oka, T. & Mihara, K. Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. EMBO J. 25, 2966–2977 (2006).",{"doi":6062},"10.1038\u002Fsj.emboj.7601184",{"id":24,"text":6064,"url":24,"identifiers":6065},"Ehses, S. et al. Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. J. Cell Biol. 187, 1023–1036 (2009).",{"doi":6066},"10.1083\u002Fjcb.200906084",{"id":24,"text":6068,"url":24,"identifiers":6069},"Song, Z., Chen, H., Fiket, M., Alexander, C. & Chan, D. C. OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J. Cell Biol. 178, 749–755 (2007).",{"doi":6070},"10.1083\u002Fjcb.200704110",{"id":24,"text":6072,"url":24,"identifiers":6073},"Head, B., Griparic, L., Amiri, M., Gandre-Babbe, S. & van der Bliek, A. M. Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells. J. Cell Biol. 187, 959–966 (2009).",{"doi":6074},"10.1083\u002Fjcb.200906083",{"id":24,"text":6076,"url":24,"identifiers":6077},"Wong, E. D. et al. The dynamin-related GTPase, Mgm1p, is an intermembrane space protein required for maintenance of fusion competent mitochondria. J. Cell Biol. 151, 341–352 (2000).",{"doi":6078},"10.1083\u002Fjcb.151.2.341",{"id":24,"text":6080,"url":24,"identifiers":6081},"Chen, H. et al. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J. Cell Biol. 160, 189–200 (2003). Demonstrates that both mammalian mitofusin isoforms are required to promote mitochondrial fusion and play essential parts in development.",{"doi":6082},"10.1083\u002Fjcb.200211046",{"id":24,"text":6084,"url":24,"identifiers":6085},"Olichon, A. et al. Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J. Biol. Chem. 278, 7743–7746 (2003).",{"doi":6086},"10.1074\u002Fjbc.C200677200",{"id":24,"text":6088,"url":24,"identifiers":6089},"Meeusen, S., McCaffery, J. M. & Nunnari, J. Mitochondrial fusion intermediates revealed in vitro. Science 305, 1747–1752 (2004). Describes an in vitro assay that was used to dissect distinct steps of mitochondrial double-membrane fusion.",{"doi":6090},"10.1126\u002Fscience.1100612",{"id":24,"text":6092,"url":24,"identifiers":6093},"Koshiba, T. et al. Structural basis of mitochondrial tethering by mitofusin complexes. Science 305, 858–862 (2004).",{"doi":6094},"10.1126\u002Fscience.1099793",{"id":24,"text":6096,"url":24,"identifiers":6097},"DeVay, R. M. et al. Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion. J. Cell Biol. 186, 793–803 (2009).",{"doi":6098},"10.1083\u002Fjcb.200906098",{"id":24,"text":6100,"url":24,"identifiers":6101},"Malka, F. et al. Separate fusion of outer and inner mitochondrial membranes. EMBO Rep. 6, 853–859 (2005).",{"doi":6102},"10.1038\u002Fsj.embor.7400488",{"id":24,"text":6104,"url":24,"identifiers":6105},"Sesaki, H. & Jensen, R. E. UGO1 encodes an outer membrane protein required for mitochondrial fusion. J. Cell Biol. 152, 1123–1134 (2001).",{"doi":6106},"10.1083\u002Fjcb.152.6.1123",{"id":24,"text":6108,"url":24,"identifiers":6109},"Hoppins, S., Horner, J., Song, C., McCaffery, J. M. & Nunnari, J. Mitochondrial outer and inner membrane fusion requires a modified carrier protein. J. Cell Biol. 184, 569–581 (2009).",{"doi":6110},"10.1083\u002Fjcb.200809099",{"id":24,"text":6112,"url":24,"identifiers":6113},"Sesaki, H. & Jensen, R. E. Ugo1p links the Fzo1p and Mgm1p GTPases for mitochondrial fusion. J. Biol. Chem. 279, 28298–28303 (2004).",{"doi":6114},"10.1074\u002Fjbc.M401363200",{"id":24,"text":6116,"url":24,"identifiers":6117},"Praefcke, G. J. & McMahon, H. T. The dynamin superfamily: universal membrane tubulation and fission molecules? Nature Rev. Mol. Cell Biol. 5, 133–147 (2004).",{"doi":6118},"10.1038\u002Fnrm1313",{"id":24,"text":6120,"url":24,"identifiers":6121},"Smirnowa, E., Shurland, D. L., Ryazantsev, S. N. & van der Bliek, A. M. A human dynamin-related protein controls the distribution of mitochondria. J. Cell Biol. 143, 351–358 (1998).",{"doi":6122},"10.1083\u002Fjcb.143.2.351",{"id":24,"text":6124,"url":24,"identifiers":6125},"Otsuga, D. et al. The dynamin-related GTPase, Dnm1p, controls mitochondrial morphology in yeast. J. Cell Biol. 143, 333–349 (1998).",{"doi":6126},"10.1083\u002Fjcb.143.2.333",{"id":24,"text":6128,"url":24,"identifiers":6129},"Mozdy, A., McCaffery, J. M. & Shaw, J. M. Dnm1p GTPase-mediated mitochondrial fusion is a multi-step process requiring the novel integral membrane component Fis1p. J. Cell Biol. 151, 367–379 (2000).",{"doi":6130},"10.1083\u002Fjcb.151.2.367",{"id":24,"text":6132,"url":24,"identifiers":6133},"Tieu, Q. & Nunnari, J. Mdv1p is a WD repeat protein that interacts with the dynamin-related GTPase, Dnm1p, to trigger mitochondrial division. J. Cell Biol. 151, 353–365 (2000).",{"doi":6134},"10.1083\u002Fjcb.151.2.353",{"id":24,"text":6136,"url":24,"identifiers":6137},"Zhang, Y. & Chan, D. C. Structural basis for recruitment of mitochondrial fission complexes by Fis1. Proc. Natl Acad. Sci. USA 104, 18526–18530 (2007).",{"doi":6138},"10.1073\u002Fpnas.0706441104",{"id":24,"text":6140,"url":24,"identifiers":6141},"Tieu, Q., Okreglak, V., Naylor, K. & Nunnari, J. The WD repeat protein, Mdv1p, functions as a molecular adaptor by interacting with Dnm1p and Fis1p during mitochondrial fission. J. Cell Biol. 158, 445–452 (2002).",{"doi":6142},"10.1083\u002Fjcb.200205031",{"id":24,"text":6144,"url":24,"identifiers":6145},"Lackner, L. L., Horner, J. S. & Nunnari, J. Mechanistic analysis of a dynamin effector. Science 325, 874–877 (2009).",{"doi":6146},"10.1126\u002Fscience.1176921",{"id":24,"text":6148,"url":24,"identifiers":6149},"Ingerman, E. et al. Dnm1 forms spirals that are structurally tailored to fit mitochondria. J. Cell Biol. 170, 1021–1027 (2005). References 44 and 45 report in vitro studies providing mechanistic insights into the self-assembly of Dnm1 into helical structures that are thought to drive membrane scission.",{"doi":6150},"10.1083\u002Fjcb.200506078",{"id":24,"text":6152,"url":24,"identifiers":6153},"Griffin, E. E., Graumann, J. & Chan, D. C. The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondria. J. Cell Biol. 170, 237–248 (2005).",{"doi":6154},"10.1083\u002Fjcb.200503148",{"id":24,"text":6156,"url":24,"identifiers":6157},"Schauss, A. C., Bewersdorf, J. & Jakobs, S. Fis1p and Caf4p, but not Mdv1p, determine the polar localization of Dnm1p clusters on the mitochondrial surface. J. Cell Sci. 119, 3098–3106 (2006).",{"doi":6158},"10.1242\u002Fjcs.03026",{"id":24,"text":6160,"url":24,"identifiers":6161},"Dimmer, K. S. et al. Genetic basis of mitochondrial function and morphology in Saccharomyces cerevisiae. Mol. Biol. Cell 13, 847–853 (2002). Describes a systematic, genome-wide screen in yeast that led to the discovery of several genes affecting mitochondrial dynamics, including MDM30, MDM33, MDM36, NUM1 and PCP1.",{"doi":6162},"10.1091\u002Fmbc.01-12-0588",{"id":24,"text":6164,"url":24,"identifiers":6165},"Cerveny, K. L., Studer, S. L., Jensen, R. E. & Sesaki, H. Yeast mitochondrial division and distribution require the cortical Num1 protein. Dev. Cell 12, 363–375 (2007).",{"doi":6166},"10.1016\u002Fj.devcel.2007.01.017",{"id":24,"text":6168,"url":24,"identifiers":6169},"Hammermeister, M., Schödel, K. & Westermann, B. Mdm36 is a mitochondrial fission-promoting protein in Saccharomyces cerevisiae. Mol. Biol. Cell 21, 2443–2452 (2010).",{"doi":6170},"10.1091\u002Fmbc.e10-02-0096",{"id":24,"text":6172,"url":24,"identifiers":6173},"Roux, A., Uyhazi, K., Frost, A. & De Camilli, P. GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission. Nature 441, 528–531 (2006).",{"doi":6174},"10.1038\u002Fnature04718",{"id":24,"text":6176,"url":24,"identifiers":6177},"Yoon, Y., Krueger, E. W., Oswald, B. J. & McNiven, M. A. The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol. Cell. Biol. 23, 5409–5420 (2003).",{"doi":6178},"10.1128\u002FMCB.23.15.5409-5420.2003",{"id":24,"text":6180,"url":24,"identifiers":6181},"James, D. I., Parone, P. A., Mattenberger, Y. & Martinou, J. C. hFis1, a novel component of the mammalian mitochondrial fission machinery. J. Biol. Chem. 278, 36373–36379 (2003).",{"doi":6182},"10.1074\u002Fjbc.M303758200",{"id":24,"text":6184,"url":24,"identifiers":6185},"Lee, Y. J., Jeong, S. Y., Karbowski, M., Smith, C. L. & Youle, R. J. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. Mol. Biol. Cell 15, 5001–5011 (2004).",{"doi":6186},"10.1091\u002Fmbc.e04-04-0294",{"id":24,"text":6188,"url":24,"identifiers":6189},"Breckenridge, D. G. et al. Caenorhabditis elegans drp-1 and fis-2 regulate distinct cell-death execution pathways downstream of ced-3 and independent of ced-9. Mol. Cell 31, 586–597 (2008).",{"doi":6190},"10.1016\u002Fj.molcel.2008.07.015",{"id":24,"text":6192,"url":24,"identifiers":6193},"Gandre-Babbe, S. & van der Bliek, A. M. The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. Mol. Biol. Cell 19, 2402–2412 (2008).",{"doi":6194},"10.1091\u002Fmbc.e07-12-1287",{"id":24,"text":6196,"url":24,"identifiers":6197},"Labrousse, A. M., Zappaterra, M. D., Rube, D. A. & van der Bliek, A. M. C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. Mol. Cell 4, 815–826 (1999).",{"doi":6198},"10.1016\u002FS1097-2765(00)80391-3",{"id":24,"text":6200,"url":24,"identifiers":6201},"Legesse-Miller, A., Massol, R. H. & Kirchhausen, T. Constriction and Dnm1p recruitment are distinct processes in mitochondrial fission. Mol. Biol. Cell 14, 1953–1963 (2003).",{"doi":6202},"10.1091\u002Fmbc.e02-10-0657",{"id":24,"text":6204,"url":24,"identifiers":6205},"Jakobs, S. et al. Spatial and temporal dynamics of budding yeast mitochondria lacking the division component Fis1p. J. Cell Sci. 116, 2005–2014 (2003).",{"doi":6206},"10.1242\u002Fjcs.00423",{"id":24,"text":6208,"url":24,"identifiers":6209},"Messerschmitt, M. et al. The inner membrane protein Mdm33 controls mitochondrial morphology in yeast. J. Cell Biol. 160, 553–564 (2003).",{"doi":6210},"10.1083\u002Fjcb.200211113",{"id":24,"text":6212,"url":24,"identifiers":6213},"Tondera, D. et al. The mitochondrial protein MTP18 contributes to mitochondrial fission in mammalian cells. J. Cell Sci. 118, 3049–3059 (2005).",{"doi":6214},"10.1242\u002Fjcs.02415",{"id":24,"text":6216,"url":24,"identifiers":6217},"Sesaki, H. & Jensen, R. E. Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape. J. Cell Biol. 147, 699–706 (1999).",{"doi":6218},"10.1083\u002Fjcb.147.4.699",{"id":24,"text":6220,"url":24,"identifiers":6221},"Bleazard, W. et al. The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nature Cell Biol. 1, 298–304 (1999). References 62 and 63 show in yeast that fusion and fission are antagonistic and balanced activities that are both required for the maintenance of mitochondrial morphology.",{"doi":6222},"10.1038\u002F13014",{"id":24,"text":6224,"url":24,"identifiers":6225},"Fritz, S., Weinbach, N. & Westermann, B. Mdm30 is an F-box protein required for maintenance of fusion-competent mitochondria in yeast. Mol. Biol. Cell 14, 2303–2313 (2003).",{"doi":6226},"10.1091\u002Fmbc.e02-12-0831",{"id":24,"text":6228,"url":24,"identifiers":6229},"Cohen, M. M., Leboucher, G. P., Livnat-Levanon, N., Glickman, M. H. & Weissman, A. M. Ubiquitin-proteasome-dependent degradation of a mitofusin, a critical regulator of mitochondrial fusion. Mol. Biol. Cell 19, 2457–2464 (2008).",{"doi":6230},"10.1091\u002Fmbc.e08-02-0227",{"id":24,"text":6232,"url":24,"identifiers":6233},"Amiott, E. A., Cohen, M. M., Saint-Georges, Y., Weissman, A. M. & Shaw, J. M. A mutation associated with CMT2A neuropathy causes defects in Fzo1 GTP hydrolysis, ubiquitylation, and protein turnover. Mol. Biol. Cell 20, 5026–5035 (2009).",{"doi":6234},"10.1091\u002Fmbc.e09-07-0622",{"id":24,"text":6236,"url":24,"identifiers":6237},"Herlan, M., Bornhövd, C., Hell, K., Neupert, W. & Reichert, A. S. Alternative topogenesis of Mgm1 and mitochondrial morphology depend on ATP and a functional import motor. J. Cell Biol. 165, 167–173 (2004). Formulation of an attractive hypothesis that suggests that alternative processing of Mgm1 could adapt mitochondrial fusion rates to matrix ATP levels.",{"doi":6238},"10.1083\u002Fjcb.200403022",{"id":24,"text":6240,"url":24,"identifiers":6241},"Baricault, L. et al. OPA1 cleavage depends on decreased mitochondrial ATP level and bivalent metals. Exp. Cell Res. 313, 3800–3808 (2007).",{"doi":6242},"10.1016\u002Fj.yexcr.2007.08.008",{"id":24,"text":6244,"url":24,"identifiers":6245},"Nakamura, N., Kimura, Y., Tokuda, M., Honda, S. & Hirose, S. MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to change mitochondrial morphology. EMBO Rep. 7, 1019–1022 (2006).",{"doi":6246},"10.1038\u002Fsj.embor.7400790",{"id":24,"text":6248,"url":24,"identifiers":6249},"Karbowski, M., Neutzner, A. & Youle, R. J. The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division. J. Cell Biol. 178, 71–84 (2007).",{"doi":6250},"10.1083\u002Fjcb.200611064",{"id":24,"text":6252,"url":24,"identifiers":6253},"Yonashiro, R. et al. A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics. EMBO J. 25, 3618–3626 (2006).",{"doi":6254},"10.1038\u002Fsj.emboj.7601249",{"id":24,"text":6256,"url":24,"identifiers":6257},"Park, Y. Y. et al. Loss of MARCH5 mitochondrial E3 ubiquitin ligase induces cellular senescence through dynamin-related protein 1 and mitofusin 1. J. Cell Sci. 123, 619–626 (2010).",{"doi":6258},"10.1242\u002Fjcs.061481",{"id":24,"text":6260,"url":24,"identifiers":6261},"Braschi, E., Zunino, R. & McBride, H. M. MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission. EMBO Rep. 10, 748–754 (2009).",{"doi":6262},"10.1038\u002Fembor.2009.86",{"id":24,"text":6264,"url":24,"identifiers":6265},"Zunino, R., Schauss, A., Rippstein, P., Andrade-Navarro, M. & McBride, H. M. The SUMO protease SENP5 is required to maintain mitochondrial morphology and function. J. Cell Sci. 120, 1178–1188 (2007).",{"doi":6266},"10.1242\u002Fjcs.03418",{"id":24,"text":6268,"url":24,"identifiers":6269},"Taguchi, N., Ishihara, N., Jofuku, A., Oka, T. & Mihara, K. Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission. J. Biol. Chem. 282, 11521–11529 (2007).",{"doi":6270},"10.1074\u002Fjbc.M607279200",{"id":24,"text":6272,"url":24,"identifiers":6273},"Cribbs, J. T. & Strack, S. Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep. 8, 939–944 (2007).",{"doi":6274},"10.1038\u002Fsj.embor.7401062",{"id":24,"text":6276,"url":24,"identifiers":6277},"Han, X. J. et al. CaM kinase I α-induced phosphorylation of Drp1 regulates mitochondrial morphology. J. Cell Biol. 182, 573–585 (2008).",{"doi":6278},"10.1083\u002Fjcb.200802164",{"id":24,"text":6280,"url":24,"identifiers":6281},"Cereghetti, G. M. et al. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc. Natl Acad. Sci. USA 105, 15803–15808 (2008).",{"doi":6282},"10.1073\u002Fpnas.0808249105",{"id":24,"text":6284,"url":24,"identifiers":6285},"Eura, Y., Ishihara, N., Oka, T. & Mihara, K. Identification of a novel protein that regulates mitochondrial fusion by modulating mitofusin (Mfn) protein function. J. Cell Sci. 119, 4913–4925 (2006).",{"doi":6286},"10.1242\u002Fjcs.03253",{"id":24,"text":6288,"url":24,"identifiers":6289},"Liesa, M. et al. Mitochondrial fusion is increased by the nuclear coactivator PGC-1β. PLoS One 3, e3613 (2008).",{"doi":6290},"10.1371\u002Fjournal.pone.0003613",{"id":24,"text":6292,"url":24,"identifiers":6293},"Karbowski, M., Norris, K. L., Cleland, M. M., Jeong, S. Y. & Youle, R. J. Role of Bax and Bak in mitochondrial morphogenesis. Nature 443, 658–662 (2006).",{"doi":6294},"10.1038\u002Fnature05111",{"id":24,"text":6296,"url":24,"identifiers":6297},"Chen, X. J. & Butow, R. A. The organization and inheritance of the mitochondrial genome. Nature Rev. Genet. 6, 815–825 (2005).",{"doi":6298},"10.1038\u002Fnrg1708",{"id":24,"text":6300,"url":24,"identifiers":6301},"Pfanner, N. & Geissler, A. Versatility of the mitochondrial protein import machinery. Nature Rev. Mol. Cell. Biol. 2, 339–349 (2001).",{"doi":6302},"10.1038\u002F35073006",{"id":24,"text":6304,"url":24,"identifiers":6305},"Neupert, W. & Herrmann, J. M. Translocation of proteins into mitochondria. Annu. Rev. Biochem. 76, 723–749 (2007).",{"doi":6306},"10.1146\u002Fannurev.biochem.76.052705.163409",{"id":24,"text":6308,"url":24,"identifiers":6309},"Ishihara, N. et al. Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. Nature Cell Biol. 11, 958–966 (2009).",{"doi":6310},"10.1038\u002Fncb1907",{"id":24,"text":6312,"url":24,"identifiers":6313},"Altmann, K., Frank, M., Neumann, D., Jakobs, S. & Westermann, B. The class V myosin motor protein, Myo2, plays a major role in mitochondrial motility in Saccharomyces cerevisiae. J. Cell Biol. 181, 119–130 (2008).",{"doi":6314},"10.1083\u002Fjcb.200709099",{"id":24,"text":6316,"url":24,"identifiers":6317},"Wakabayashi, J. et al. The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J. Cell Biol. 186, 805–816 (2009). References 85 and 87 show that DRP1-dependent fission and distribution of mitochondria is essential in embryonic and brain development in mice.",{"doi":6318},"10.1083\u002Fjcb.200903065",{"id":24,"text":6320,"url":24,"identifiers":6321},"Merz, S. & Westermann, B. Genome-wide deletion mutant analysis reveals genes required for respiratory growth, mitochondrial genome maintenance and mitochondrial protein synthesis in Saccharomyces cerevisiae. Genome Biol. 10, R95 (2009).",{"doi":6322},"10.1186\u002Fgb-2009-10-9-r95",{"id":24,"text":6324,"url":24,"identifiers":6325},"Chen, H., Chomyn, A. & Chan, D. C. Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J. Biol. Chem. 280, 26185–26192 (2005).",{"doi":6326},"10.1074\u002Fjbc.M503062200",{"id":24,"text":6328,"url":24,"identifiers":6329},"Chen, H., McCaffery, J. M. & Chan, D. C. Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell 130, 548–562 (2007).",{"doi":6330},"10.1016\u002Fj.cell.2007.06.026",{"id":24,"text":6332,"url":24,"identifiers":6333},"Li, Z., Okamoto, K., Hayashi, Y. & Sheng, M. The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119, 873–887 (2004). References 90 and 91 show that mitochondrial dynamics is crucial for neuronal development and function.",{"doi":6334},"10.1016\u002Fj.cell.2004.11.003",{"id":24,"text":6336,"url":24,"identifiers":6337},"Amchenkova, A. A., Bakeeva, L. E., Chentsov, Y. S., Skulachev, V. P. & Zorov, D. B. Coupling membranes as energy-transmitting cables. I. Filamentous mitochondria in fibroblasts and mitochondrial clusters in cardiomyocytes. J. Cell Biol. 107, 481–495 (1988).",{"doi":6338},"10.1083\u002Fjcb.107.2.481",{"id":24,"text":6340,"url":24,"identifiers":6341},"Tondera, D. et al. SLP-2 is required for stress-induced mitochondrial hyperfusion. EMBO J. 28, 1589–1600 (2009).",{"doi":6342},"10.1038\u002Femboj.2009.89",{"id":24,"text":6344,"url":24,"identifiers":6345},"Mitra, K., Wunder, C., Roysam, B., Lin, G. & Lippincott-Schwartz, J. A hyperfused mitochondrial state achieved at G1-S regulates cyclin E buildup and entry into S phase. Proc. Natl Acad. Sci. USA 106, 11960–11965 (2009).",{"doi":6346},"10.1073\u002Fpnas.0904875106",{"id":24,"text":6348,"url":24,"identifiers":6349},"Balaban, R. S., Nemoto, S. & Finkel, T. Mitochondria, oxidants, and aging. Cell 120, 483–495 (2005).",{"doi":6350},"10.1016\u002Fj.cell.2005.02.001",{"id":24,"text":6352,"url":24,"identifiers":6353},"Ono, T., Isobe, K., Nakada, K. & Hayashi, J. I. Human cells are protected from mitochondrial dysfunction by complementation of DNA products in fused mitochondria. Nature Genet. 28, 272–275 (2001). Shows that complementation of gene products in fused mitochondria restores respiratory activity in heteroplasmic cells.",{"doi":6354},"10.1038\u002F90116",{"id":24,"text":6356,"url":24,"identifiers":6357},"Nakada, K. et al. Inter-mitochondrial complementation: mitochondria-specific system preventing mice from expression of disease phenotypes by mutant mtDNA. Nature Med. 7, 934–940 (2001).",{"doi":6358},"10.1038\u002F90976",{"id":24,"text":6360,"url":24,"identifiers":6361},"Chen, H. et al. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell 141, 280–289 (2010). Shows that mitochondrial fusion is required for the maintenance of functional mitochondria in muscle cells.",{"doi":6362},"10.1016\u002Fj.cell.2010.02.026",{"id":24,"text":6364,"url":24,"identifiers":6365},"He, C. & Klionsky, D. J. Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. Genet. 43, 67–93 (2009).",{"doi":6366},"10.1146\u002Fannurev-genet-102808-114910",{"id":24,"text":6368,"url":24,"identifiers":6369},"Twig, G. et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 27, 433–446 (2008). Suggests a functional connection between mitochondrial dynamics and the removal of impaired mitochondria by mitophagy.",{"doi":6370},"10.1038\u002Fsj.emboj.7601963",{"id":24,"text":6372,"url":24,"identifiers":6373},"Youle, R. J. & Karbowski, M. Mitochondrial fission in apoptosis. Nature Rev. Mol. Cell Biol. 6, 657–663 (2005).",{"doi":6374},"10.1038\u002Fnrm1697",{"id":24,"text":6376,"url":24,"identifiers":6377},"Suen, D. F., Norris, K. L. & Youle, R. J. Mitochondrial dynamics and apoptosis. Genes Dev. 22, 1577–1590 (2008).",{"doi":6378},"10.1101\u002Fgad.1658508",{"id":24,"text":6380,"url":24,"identifiers":6381},"Fannjiang, Y. et al. Mitochondrial fission proteins regulate programmed cell death in yeast. Genes Dev. 18, 2785–2797 (2004).",{"doi":6382},"10.1101\u002Fgad.1247904",{"id":24,"text":6384,"url":24,"identifiers":6385},"Jagasia, R., Grote, P., Westermann, B. & Conradt, B. DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death in C. elegans. Nature 433, 754–760 (2005).",{"doi":6386},"10.1038\u002Fnature03316",{"id":24,"text":6388,"url":24,"identifiers":6389},"Goyal, G., Fell, B., Sarin, A., Youle, R. J. & Sriram, V. Role of mitochondrial remodeling in programmed cell death in Drosophila melanogaster. Dev. Cell 12, 807–816 (2007).",{"doi":6390},"10.1016\u002Fj.devcel.2007.02.002",{"id":24,"text":6392,"url":24,"identifiers":6393},"Frank, S. et al. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev. Cell 1, 515–525 (2001). First report demonstrating a role for DRP1 in apoptosis.",{"doi":6394},"10.1016\u002FS1534-5807(01)00055-7",{"id":24,"text":6396,"url":24,"identifiers":6397},"Brooks, C. et al. Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins. Proc. Natl Acad. Sci. USA 104, 11649–11654 (2007).",{"doi":6398},"10.1073\u002Fpnas.0703976104",{"id":24,"text":6400,"url":24,"identifiers":6401},"Karbowski, M. et al. Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis. J. Cell Biol. 159, 931–938 (2002).",{"doi":6402},"10.1083\u002Fjcb.200209124",{"id":24,"text":6404,"url":24,"identifiers":6405},"Wasiak, S., Zunino, R. & McBride, H. M. Bax\u002FBak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death. J. Cell Biol. 177, 439–450 (2007).",{"doi":6406},"10.1083\u002Fjcb.200610042",{"id":24,"text":6408,"url":24,"identifiers":6409},"Knott, A. B., Perkins, G., Schwarzenbacher, R. & Bossy-Wetzel, E. Mitochondrial fragmentation in neurodegeneration. Nature Rev. Neurosci. 9, 505–518 (2008).",{"doi":6410},"10.1038\u002Fnrn2417",{"id":24,"text":6412,"url":24,"identifiers":6413},"Alexander, C. et al. OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant atrophy linked to chromosome 3q28. Nature Genet. 26, 211–215 (2000).",{"doi":6414},"10.1038\u002F79944",{"id":24,"text":6416,"url":24,"identifiers":6417},"Delettre, C. et al. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nature Genet. 26, 207–210 (2000).",{"doi":6418},"10.1038\u002F79936",{"id":24,"text":6420,"url":24,"identifiers":6421},"Züchner, S. et al. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nature Genet. 36, 449–451 (2004).",{"doi":6422},"10.1038\u002Fng1341",{"id":24,"text":6424,"url":24,"identifiers":6425},"Waterham, H. R. et al. A lethal defect of mitochondrial and peroxisomal fission. N. Engl. J. Med. 356, 1736–1741 (2007).",{"doi":6426},"10.1056\u002FNEJMoa064436",{"id":24,"text":6428,"url":24,"identifiers":6429},"Narendra, D. P. et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 8, e1000298 (2010).",{"doi":6430},"10.1371\u002Fjournal.pbio.1000298",{"id":24,"text":6432,"url":24,"identifiers":6433},"Matsuda, N. et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J. Cell Biol. 189, 211–221 (2010).",{"doi":6434},"10.1083\u002Fjcb.200910140",{"id":24,"text":6436,"url":24,"identifiers":6437},"Deng, H., Dodson, M. W., Huang, H. & Guo, M. The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and\u002For inhibit fusion in Drosophila. Proc. Natl Acad. Sci. USA 105, 14503–14508 (2008).",{"doi":6438},"10.1073\u002Fpnas.0803998105",{"id":24,"text":6440,"url":24,"identifiers":6441},"Yang, Y. et al. Pink1 regulates mitochondrial dynamics through interaction with the fission\u002Ffusion machinery. Proc. Natl Acad. Sci. USA 105, 7070–7075 (2008).",{"doi":6442},"10.1073\u002Fpnas.0711845105",{"id":24,"text":6444,"url":24,"identifiers":6445},"Ziviani, E., Tao, R. N. & Whitworth, A. J. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc. Natl Acad. Sci. USA 107, 5018–5023 (2010).",{"doi":6446},"10.1073\u002Fpnas.0913485107",{"id":24,"text":6448,"url":24,"identifiers":6449},"Lutz, A. K. et al. Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J. Biol. Chem. 284, 22938–22951 (2009).",{"doi":6450},"10.1074\u002Fjbc.M109.035774",{"id":24,"text":6452,"url":24,"identifiers":6453},"Kuravi, K. et al. Dynamin-related proteins Vps1p and Dnm1p control peroxisome abundance in Saccharomyces cerevisiae. J. Cell Sci. 119, 3994–4001 (2006).",{"doi":6454},"10.1242\u002Fjcs.03166",{"id":24,"text":6456,"url":24,"identifiers":6457},"Koch, A. et al. Dynamin-like protein 1 is involved in peroxisomal fission. J. Biol. Chem. 278, 8597–8605 (2003).",{"doi":6458},"10.1074\u002Fjbc.M211761200",{"id":24,"text":6460,"url":24,"identifiers":6461},"Koch, A., Yoon, Y., Bonekamp, N. A., McNiven, M. A. & Schrader, M. A role for Fis1 in both mitochondrial and peroxisomal fission in mammalian cells. Mol. Biol. Cell 16, 5077–5086 (2005).",{"doi":6462},"10.1091\u002Fmbc.e05-02-0159",{"id":24,"text":6464,"url":24,"identifiers":6465},"Neuspiel, M. et al. Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers. Curr. Biol. 18, 102–108 (2008).",{"doi":6466},"10.1016\u002Fj.cub.2007.12.038",{"id":24,"text":6468,"url":24,"identifiers":6469},"Martins de Brito, O. & Scorrano, L. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456, 605–610 (2008).",{"doi":6470},"10.1038\u002Fnature07534",{"id":24,"text":6472,"url":24,"identifiers":6473},"Hailey, D. W. et al. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141, 656–667 (2010).",{"doi":6474},"10.1016\u002Fj.cell.2010.04.009",{"id":24,"text":6476,"url":24,"identifiers":6477},"Altmann, K. & Westermann, B. Role of essential genes in mitochondrial morphogenesis in Saccharomyces cerevisiae. Mol. Biol. Cell 16, 5410–5417 (2005).",{"doi":6478},"10.1091\u002Fmbc.e05-07-0678",{"id":24,"text":6480,"url":24,"identifiers":6481},"Arimura, S., Yamamoto, J., Aida, G. P., Nakazono, M. & Tsutsumi, N. Frequent fusion and fission of plant mitochondria with unequal nucleoid distribution. Proc. Natl Acad. Sci. USA 101, 7805–7808 (2004).",{"doi":6482},"10.1073\u002Fpnas.0401077101",{"id":24,"text":6484,"url":24,"identifiers":6485},"Arimura, S. & Tsutsumi, N. A dynamin-like protein (ADL2b), rather than FtsZ, is involved in Arabidopsis mitochondrial division. Proc. Natl Acad. Sci. USA 99, 5727–5731 (2002).",{"doi":6486},"10.1073\u002Fpnas.082663299",{"id":24,"text":6488,"url":24,"identifiers":6489},"Logan, D. C., Scott, I. & Tobin, A. K. ADL2a, like ADL2b, is involved in the control of higher plant mitochondrial morphology. J. Exp. Bot. 55, 783–785 (2004).",{"doi":6490},"10.1093\u002Fjxb\u002Ferh073",{"id":24,"text":6492,"url":24,"identifiers":6493},"Scott, I., Tobin, A. K. & Logan, D. C. BIGYIN, an orthologue of human and yeast FIS1 genes functions in the control of mitochondrial size and number in Arabidopsis thaliana. J. Exp. Bot. 57, 1275–1280 (2006).",{"doi":6494},"10.1093\u002Fjxb\u002Ferj096",{"id":24,"text":6496,"url":24,"identifiers":6497},"Arimura, S. et al. Arabidopsis elongated mitochondria1 is required for localization of dynamin-related protein 3a to mitochondrial fission sites. Plant Cell 20, 1555–1566 (2008).",{"doi":6498},"10.1105\u002Ftpc.108.058578",{"id":24,"text":6500,"url":24,"identifiers":6501},"Beech, P. L. et al. Mitochondrial FtsZ in a chromophyte alga. Science 287, 1276–1279 (2000).",{"doi":6502},"10.1126\u002Fscience.287.5456.1276",{"id":24,"text":6504,"url":24,"identifiers":6505},"Takahara, M. et al. A putative mitochondrial ftsZ gene is present in the unicellular primitive red alga Cyanidioschyzon merolae. Mol. Gen. Genet. 264, 452–460 (2000).",{"doi":6506},"10.1007\u002Fs004380000307"]