Targeting the Ubiquitin System in Glioblastoma
Tóm tắt
Glioblastoma is the most common primary brain tumor in adults with poor overall outcome and 5-year survival of less than 5%. Treatment has not changed much in the last decade or so, with surgical resection and radio/chemotherapy being the main options. Glioblastoma is highly heterogeneous and frequently becomes treatment-resistant due to the ability of glioblastoma cells to adopt stem cell states facilitating tumor recurrence. Therefore, there is an urgent need for novel therapeutic strategies. The ubiquitin system, in particular E3 ubiquitin ligases and deubiquitinating enzymes, have emerged as a promising source of novel drug targets. In addition to conventional small molecule drug discovery approaches aimed at modulating enzyme activity, several new and exciting strategies are also being explored. Among these, PROteolysis TArgeting Chimeras (PROTACs) aim to harness the endogenous protein turnover machinery to direct therapeutically relevant targets, including previously considered “undruggable” ones, for proteasomal degradation. PROTAC and other strategies targeting the ubiquitin proteasome system offer new therapeutic avenues which will expand the drug development toolboxes for glioblastoma. This review will provide a comprehensive overview of E3 ubiquitin ligases and deubiquitinating enzymes in the context of glioblastoma and their involvement in core signaling pathways including EGFR, TGF-β, p53 and stemness-related pathways. Finally, we offer new insights into how these ubiquitin-dependent mechanisms could be exploited therapeutically for glioblastoma.
Từ khóa
Tài liệu tham khảo
Louis, 2016, The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary, Acta Neuropathol, 131, 10.1007/s00401-016-1545-1
Ostrom, 2013, CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010, Neuro Oncol, ii1, 10.1093/neuonc/not151
Louis, 2007, The 2007 WHO classification of tumours of the central nervous system, Acta Neuropathol, 114, 97, 10.1007/s00401-007-0243-4
Ohgaki, 2013, The definition of primary and secondary glioblastoma, Clin Cancer Res, 19, 10.1158/1078-0432.CCR-12-3002
Dang, 2009, Cancer-associated IDH1 mutations produce 2-hydroxyglutarate, Nature, 462, 10.1038/nature08617
Lu, 2012, IDH mutation impairs histone demethylation and results in a block to cell differentiation, Nature, 483, 10.1038/nature10860
Toyota, 1999, CpG island methylator phenotype in colorectal cancer, Proc Natl Acad Sci USA, 96, 10.1073/pnas.96.15.8681
Turcan, 2012, IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype, Nature, 483, 10.1038/nature10866
Unruh, 2019, Methylation and transcription patterns are distinct in IDH mutant gliomas compared to other IDH mutant cancers, Sci Rep, 9, 8946, 10.1038/s41598-019-45346-1
Nakamura, 2001, Promoter hypermethylation of the RB1 gene in glioblastomas, Lab Invest, 81, 77, 10.1038/labinvest.3780213
Martinez, 2009, A microarray-based DNA methylation study of glioblastoma multiforme, Epigenetics, 4, 10.4161/epi.9130
Kim, 2006, Epigenomic profiling reveals novel and frequent targets of aberrant DNA methylation-mediated silencing in malignant glioma, Cancer Res, 66, 10.1158/0008-5472.CAN-05-4552
Uhlmann, 2003, Distinct methylation profiles of glioma subtypes, Int J Cancer, 106, 10.1002/ijc.11175
Nakamura, 2001, Promoter methylation of the DNA repair gene MGMT in astrocytomas is frequently associated with G:C → A:T mutations of the TP53 tumor suppressor gene, Carcinogenesis, 22, 10.1093/carcin/22.10.1715
Hegi, 2005, MGMT gene silencing and benefit from temozolomide in glioblastoma, N Engl J Med, 352, 997, 10.1056/NEJMoa043331
Esteller, 2000, Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents, N Engl J Med, 343, 10.1056/NEJM200011093431901
Esteller, 1999, Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia, Cancer Res, 59
Cahill, 2007, Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment, Clin Cancer Res, 13, 10.1158/1078-0432.CCR-06-2149
Verhaak, 2010, Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1, Cancer Cell, 17, 98, 10.1016/j.ccr.2009.12.020
Patel, 2014, Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma, Science, 344, 10.1126/science.1254257
Darmanis, 2017, Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma, Cell Rep, 21, 10.1016/j.celrep.2017.10.030
Stupp, 2005, Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma, N Engl J Med, 352, 10.1056/NEJMoa043330
Stupp, 2009, Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial, Lancet Oncol, 10, 10.1016/S1470-2045(09)70025-7
Stummer, 1998, Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence, Neurosurgery, 42, 10.1016/S0303-8467(97)81684-8
O’Rourke, 2017, A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma, Sci Transl Med, 9, eaaa0984, 10.1126/scitranslmed.aaa0984
Dupont, 2019, INtraoperative photoDYnamic Therapy for GliOblastomas (INDYGO): Study Protocol for a Phase I Clinical Trial, Neurosurgery, 84, 10.1093/neuros/nyy324
Brown, 2016, Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy, N Engl J Med, 375, 10.1056/NEJMoa1610497
Hilf, 2019, Actively personalized vaccination trial for newly diagnosed glioblastoma, Nature, 565, 10.1038/s41586-018-0810-y
Cohen, 2010, Will the ubiquitin system furnish as many drug targets as protein kinases, Cell, 143, 10.1016/j.cell.2010.11.016
Crews, 2010, Targeting the Undruggable Proteome: The Small Molecules of My Dreams, Chem Biol, 17, 10.1016/j.chembiol.2010.05.011
Goldstein, 1975, Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells, Proc Natl Acad Sci USA, 72, 10.1073/pnas.72.1.11
Schlesinger, 1975, The complete amino acid sequence of ubiquitin, an adenylate cyclase stimulating polypeptide probably universal in living cells, Biochemistry, 14, 10.1021/bi00681a026
Hochstrasser, 2009, Origin and function of ubiquitin-like proteins, Nature, 458, 10.1038/nature07958
van der Veen, 2012, Ubiquitin-Like Proteins, Annu Rev Biochem, 81, 10.1146/annurev-biochem-093010-153308
Jentsch, 2000, Ubiquitin and its kin: How close are the family ties, Trends Cell Biol, 10, 10.1016/S0962-8924(00)01785-2
Schulman, 2009, Ubiquitin-like protein activation by E1 enzymes: The apex for downstream signalling pathways, Nat Rev Mol Cell Biol, 10, 10.1038/nrm2673
Yuan, 2001, Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein, EMBO J, 20, 10.1093/emboj/20.3.362
Zhao, 2004, The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an, Proc Natl Acad Sci USA, 101, 10.1073/pnas.0402528101
Dastur, 2006, Herc5, an interferon-induced HECT E3 enzyme, is required for conjugation of ISG15 in human cells, J Biol Chem, 281, 10.1074/jbc.M512830200
Zou, 2006, The interferon-inducible ubiquitin-protein isopeptide ligase (E3) EFP also functions as an ISG15 E3 ligase, J Biol Chem, 281, 10.1074/jbc.M510787200
Haas, 1987, Interferon induced a 15-kilodalton protein exhibiting marked homology to ubiquitin, J Biol Chem, 262, 10.1016/S0021-9258(18)60961-5
Pearce, 2008, Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis, Science, 322, 10.1126/science.1163885
Burns, 2009, Proteasomal protein degradation in mycobacteria is dependent upon a prokaryotic ubiquitin-like protein, J Biol Chem, 284, 10.1074/jbc.M808032200
Maupin-Furlow, 2014, Prokaryotic Ubiquitin-Like Protein Modification, Annu Rev Microbiol, 68, 10.1146/annurev-micro-091313-103447
Humbard, 2010, Ubiquitin-like small archaeal modifier proteins (SAMPs) in Haloferax volcanii, Nature, 463, 54, 10.1038/nature08659
Ciechanover, 1981, Activation of the heat-stable polypeptide of the ATP-dependent proteolytic system, Proc Natl Acad Sci USA, 78, 10.1073/pnas.78.2.761
Hershko, 1980, Proposed role of ATP in protein breakdown: conjugation of protein with multiple chains of the polypeptide of ATP-dependent proteolysis, Proc Natl Acad Sci USA, 77, 10.1073/pnas.77.4.1783
Finley, 1984, Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85, Cell, 37, 43, 10.1016/0092-8674(84)90299-X
Ciechanover, 1984, Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85, Cell, 37, 57, 10.1016/0092-8674(84)90300-3
Haas, 1982, The mechanism of ubiquitin activating enzyme. A kinetic and equilibrium analysis, J Biol Chem, 257, 10.1016/S0021-9258(18)34024-9
Haas, 1982, Ubiquitin-activating enzyme. Mechanism and role in protein-ubiquitin conjugation, J Biol Chem, 257, 10.1016/S0021-9258(18)34958-5
Pickart, 1994, Substrate properties of site-specific mutant ubiquitin protein (G76a) reveal unexpected mechanistic features of ubiquitin-activating enzyme (E1), J Biol Chem, 269, 10.1016/S0021-9258(17)37255-1
Pickart, 1985, Functional heterogeneity of ubiquitin carrier proteins, J Biol Chem, 260, 10.1016/S0021-9258(18)89632-6
Wang, 2007, Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3, J Cell Biol, 177, 10.1083/jcb.200611063
Scaglione, 2013, The ubiquitin-conjugating enzyme (E2) ube2w ubiquitinates the N terminus of substrates, J Biol Chem, 288, 10.1074/jbc.C113.477596
Tatham, 2013, Ube2W conjugates ubiquitin to α-amino groups of protein N-termini, Biochem J, 453, 10.1042/BJ20130244
Hershko, 1983, Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown, J Biol Chem, 258, 10.1016/S0021-9258(20)82050-X
Scheffner, 1995, Protein ubiquitination involving an E1–E2–E3 enzyme ubiquitin thioester cascade, Nature, 373, 10.1038/373081a0
Lorick, 1999, RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination, Proc Natl Acad Sci USA, 96, 10.1073/pnas.96.20.11364
Zheng, 2000, Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases, Cell, 102, 10.1016/S0092-8674(00)00057-X
Yin, 2009, E2 interaction and dimerization in the crystal structure of TRAF6, Nat Struct Mol Biol, 16, 10.1038/nsmb.1605
Brzovic, 2001, Structure of a BRCA1-BARD1 heterodimeric RING-RING complex, Nat Struct Biol, 8, 10.1038/nsb1001-833
Eletr, 2005, E2 conjugating enzymes must disengage from their E1 enzymes before E3-dependent ubiquitin and ubiquitin-like transfer, Nat Struct Mol Biol, 12, 10.1038/nsmb984
Pruneda, 2012, Structure of an E3:E2∼Ub Complex Reveals an Allosteric Mechanism Shared among RING/U-box Ligases, Mol Cell, 47, 10.1016/j.molcel.2012.07.001
Plechanovov, 2012, Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis, Nature, 489, 10.1038/nature11376
Dou, 2012, BIRC7-E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer, Nat Struct Mol Biol, 19, 10.1038/nsmb.2379
Pruneda, 2011, Ubiquitin in Motion: Structural Studies of the Ubiquitin-Conjugating Enzyme∼Ubiquitin Conjugate, Biochemistry, 50, 10.1021/bi101913m
Eddins, 2006, Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation, Nat Struct Mol Biol, 13, 10.1038/nsmb1148
Petroski, 2005, Function and regulation of cullin-RING ubiquitin ligases, Nat Rev Mol Cell Biol, 6, 9, 10.1038/nrm1547
Ohi, 2003, Structural insights into the U-box, a domain associated with multi-ubiquitination, Nat Struct Biol, 10, 10.1038/nsb906
Aravind, 2000, The U box is a modified RING finger - A common domain in ubiquitination, Curr Biol, 10, 10.1016/S0960-9822(00)00398-5
Jiang, 2001, CHIP is a U-box-dependent E3 ubiquitin ligase: Identification of Hsc70 as a target for ubiquitylation, J Biol Chem, 276, 10.1074/jbc.M101968200
Murata, 2001, CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein, EMBO Rep, 2, 10.1093/embo-reports/kve246
Xu, 2008, Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes, BMC Struct Biol, 8, 26, 10.1186/1472-6807-8-26
Nikolay, 2004, Dimerization of the Human E3 Ligase CHIP via a Coiled-coil Domain Is Essential for Its Activity, J Biol Chem, 279, 10.1074/jbc.M311112200
Marín, 2004, Parkin and relatives: The RBR family of ubiquitin ligases, Physiol Genomics, 17, 10.1152/physiolgenomics.00226.2003
Spratt, 2014, RBR E3 Ubiquitin Ligases: New Structures, New Insights, New Questions, Biochem J, 458, 10.1042/BJ20140006
Wenzel, 2011, UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids, Nature, 474, 10.1038/nature09966
Stieglitz, 2012, LUBAC synthesizes linear ubiquitin chains via a thioester intermediate, EMBO Rep, 13, 10.1038/embor.2012.105
Smit, 2012, The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RING-IBR-RING domain and the unique LDD extension, EMBO J, 31, 10.1038/emboj.2012.217
Lazarou, 2013, PINK1 drives parkin self-association and HECT-like E3 activity upstream of mitochondrial binding, J Cell Biol, 200, 10.1083/jcb.201210111
Chew, 2011, Parkin mediates apparent E2-independent monoubiquitination in vitro and contains an intrinsic activity that catalyzes polyubiquitination, PLoS One, 6, e19720, 10.1371/journal.pone.0019720
Veeriah, 2010, Somatic Mutations of the Parkinson’s Disease-Associated Gene PARK2 in Glioblastoma and Other Human Malignancies, Nat Genet, 42, 77, 10.1038/ng.491
Matsuda, 2006, Diverse effects of pathogenic mutations of Parkin that catalyze multiple monoubiquitylation in vitro, J Biol Chem, 281, 10.1074/jbc.M510393200
Chaugule, 2011, Autoregulation of Parkin activity through its ubiquitin-like domain, EMBO J, 30, 10.1038/emboj.2011.204
Fallon, 2006, A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI(3)K-Akt signalling, Nat Cell Biol, 8, 10.1038/ncb1441
Tsai, 2003, Parkin facilitates the elimination of expanded polyglutamine proteins and leads to preservation of proteasome function, J Biol Chem, 278, 10.1074/jbc.M212235200
Marin, 2010, Animal HECT ubiquitin ligases: Evolution and functional implications, BMC Evol Biol, 10, 56, 10.1186/1471-2148-10-56
Huibregtse, 1995, family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase, Proc Natl Acad Sci USA, 92, 10.1073/pnas.92.7.2563
Scheffner, 1993, The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53, Cell, 75, 495, 10.1016/0092-8674(93)90384-3
Huibregtse, 1991, A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18, EMBO J, 10, 10.1002/j.1460-2075.1991.tb04990.x
Simonson, 2005, Two distinct activities contribute to human papillomavirus 16 E6’s oncogenic potential, Cancer Res, 65, 10.1158/0008-5472.CAN-05-1651
Scheffner, 1990, The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53, Cell, 63, 10.1016/0092-8674(90)90409-8
Kim, 2009, Polyubiquitination by HECT E3s and the Determinants of Chain Type Specificity, Mol Cell Biol, 29, 10.1128/MCB.00240-09
Huang, 1999, Structure of an E6AP-UbcH7 complex: Insights into ubiquitination by the E2-E3 enzyme cascade, Science, 286, 10.1126/science.286.5443.1321
Maspero, 2011, Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation, EMBO Rep, 12, 10.1038/embor.2011.21
Kamadurai, 2009, Insights into ubiquitin transfer cascades from a structure of a UbcH5B approximately ubiquitin-HECT(NEDD4L) complex, Mol Cell, 36, 10.1016/j.molcel.2009.11.010
Verdecia, 2003, Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase, Mol Cell, 11, 10.1016/S1097-2765(02)00774-8
Lorenz, 2018, Structural mechanisms of HECT-type ubiquitin ligases, Biol Chem, 399, 10.1515/hsz-2017-0184
Rotin, 2009, Physiological functions of the HECT family of ubiquitin ligases, Nat Rev Mol Cell Biol, 10, 398, 10.1038/nrm2690
Kumar, 1992, Identification of a set of genes with developmentally down-regulated expression in the mouse brain, Biochem Biophys Res Commun, 185, 10.1016/0006-291X(92)91747-E
Ingham, 2005, WW Domains Provide a Platform for the Assembly of Multiprotein Networks, Mol Cell Biol, 25, 10.1128/MCB.25.16.7092-7106.2005
Kanelis, 2001, Solution structure of a Nedd4 WW domain-ENaC peptide complex, Nat Struct Biol, 8, 10.1038/87562
Staub, 1996, WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle’s syndrome, EMBO J, 15, 10.1002/j.1460-2075.1996.tb00593.x
Rizo, 1998, C2-domains, structure and function of a universal Ca2+-binding domain, J Biol Chem, 273, 10.1074/jbc.273.26.15879
Tian, 2011, Binding of RhoA by the C2 domain of E3 ligase Smurf1 is essential for Smurf1-regulated RhoA ubiquitination and cell protrusive activity, FEBS Lett, 585, 10.1016/j.febslet.2011.06.016
Weber, 2019, HECT E3 ligases: A tale with multiple facets, Front Physiol, 10, 10.3389/fphys.2019.00370
Wiesner, 2007, Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain, Cell, 130, 10.1016/j.cell.2007.06.050
Attali, 2017, Ubiquitylation-dependent oligomerization regulates activity of Nedd4 ligases, EMBO J, 36, 10.15252/embj.201694314
Ronchi, 2014, The active form of E6-associated protein (E6AP)/UBE3A ubiquitin ligase is an oligomer, J Biol Chem, 289, 10.1074/jbc.M113.517805
Clague, 2019, Breaking the chains: deubiquitylating enzyme specificity begets function, Nat Rev Mol Cell Biol, 20, 10.1038/s41580-019-0099-1
Ambroggio, 2004, JAMM: A metalloprotease-like zinc site in the proteasome and signalosome, PLoS Biol, 2, e2, 10.1371/journal.pbio.0020002
Matsui, 1982, Isopeptidase: A novel eukaryotic enzyme that cleaves isopeptide bonds, Proc Natl Acad Sci USA, 79, 10.1073/pnas.79.5.1535
Miller, 1989, Cloning and expression of a yeast ubiquitin protein cleaving activity in escherichia coli, Bio/Technology, 7, 689, 10.1038/nbt0789-698
Redman, 1989, Identification of the long ubiquitin extension as ribosomal protein S27a, Nature, 338, 10.1038/338438a0
Baker, 1991, The human ubiquitin-52 amino acid fusion protein gene shares several structural features with mammalian ribosomal protein genes, Nucleic Acids Res, 19, 10.1093/nar/19.5.1035
Finley, 1987, The yeast polyubiquitin gene is essential for resistance to high temperatures, starvation, and other stresses, Cell, 48, 10.1016/0092-8674(87)90711-2
Grou, 2015, The de novo synthesis of ubiquitin: Identification of deubiquitinases acting on ubiquitin precursors, Sci Rep, 5, 1, 10.1038/srep12836
Verma, 2002, Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome, Science, 298, 10.1126/science.1075898
Williams, 2007, The emerging shape of the ESCRT machinery, Nat Rev Mol Cell Biol, 8, 10.1038/nrm2162
Finley, 2009, Recognition and Processing of Ubiquitin-Protein Conjugates by the Proteasome, Annu Rev Biochem, 78, 477, 10.1146/annurev.biochem.78.081507.101607
Worden, 2017, An AAA Motor-Driven Mechanical Switch in Rpn11 Controls Deubiquitination at the 26S Proteasome, Mol Cell, 67, 799, 10.1016/j.molcel.2017.07.023
Worden, 2014, Structure of the Rpn11-Rpn8 dimer reveals mechanisms of substrate deubiquitination during proteasomal degradation, Nat Struct Mol Biol, 21, 10.1038/nsmb.2771
de Poot, 2017, Meddling with Fate: The Proteasomal Deubiquitinating Enzymes, J Mol Biol, 429, 10.1016/j.jmb.2017.09.015
Bard, 2018, Structure and Function of the 26S Proteasome, Annu Rev Biochem, 87, 697, 10.1146/annurev-biochem-062917-011931
Emmerich, 2013, Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains, Proc Natl Acad Sci USA, 110, 10.1073/pnas.1314715110
Keusekotten, 2013, OTULIN antagonizes LUBAC signaling by specifically hydrolyzing met1-linked polyubiquitin, Cell, 153, 10.1016/j.cell.2013.05.014
Hrdinka, 2016, CYLD Limits Lys63- and Met1-Linked Ubiquitin at Receptor Complexes to Regulate Innate Immune Signaling, Cell Rep, 14, 10.1016/j.celrep.2016.02.062
Damgaard, 2016, The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity, Cell, 166, 1215, 10.1016/j.cell.2016.07.019
Wertz, 2004, De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling, Nature, 430, 10.1038/nature02794
Hershko, 1985, Occurrence of a polyubiquitin structure in ubiquitin-protein conjugates, Biochem Biophys Res Commun, 128, 10.1016/0006-291X(85)91050-2
Dahlmann, 1989, The multicatalytic proteinase (prosome) is ubiquitous from eukaryotes to archaebacteria, FEBS Lett, 251, 10.1016/0014-5793(89)81441-3
Chau, 1989, A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein, Science, 243, 10.1126/science.2538923
Hershko, 1984, ATP-dependent degradation of ubiquitin-protein conjugates, Proc Natl Acad Sci USA, 81, 10.1073/pnas.81.6.1619
Xu, 2009, Quantitative Proteomics Reveals the Function of Unconventional Ubiquitin Chains in Proteasomal Degradation, Cell, 137, 10.1016/j.cell.2009.01.041
Phu, 2011, Improved quantitative mass spectrometry methods for characterizing complex ubiquitin signals, Mol Cell Proteomics, 10, M110.003756, 10.1074/mcp.M110.003756
Deol, 2019, Enzymatic Logic of Ubiquitin Chain Assembly, Front Physiol, 10, 10.3389/fphys.2019.00835
Pickart, 1997, Targeting of substrates to the 26S proteasome, FASEB J, 11, 10.1096/fasebj.11.13.9367341
Saeki, 2009, Lysine 63-linked polyubiquitin chain may serve as a targeting signal for the 26S proteasome, EMBO J, 28, 10.1038/emboj.2008.305
Chastagner, 2006, Itch/AIP4 mediates Deltex degradation through the formation of K29-linked polyubiquitin chains, EMBO Rep, 7, 10.1038/sj.embor.7400822
Braten, 2016, Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination, Proc Natl Acad Sci USA, 113, 10.1073/pnas.1608644113
Deng, 2000, Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain, Cell, 103, 10.1016/S0092-8674(00)00126-4
Stewart, 2009, The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage, Cell, 136, 10.1016/j.cell.2008.12.042
Doil, 2009, RNF168 Binds and Amplifies Ubiquitin Conjugates on Damaged Chromosomes to Allow Accumulation of Repair Proteins, Cell, 136, 10.1016/j.cell.2008.12.041
Gatti, 2015, RNF168 promotes noncanonical K27ubiquitination to signal DNA damage, Cell Rep, 10, 10.1016/j.celrep.2014.12.021
Huang, 2013, Lysine 63-linked polyubiquitination is required for EGF receptor degradation, Proc Natl Acad Sci USA, 110, 10.1073/pnas.1308014110
Lauwers, 2009, K63-linked ubiquitin chains as a specific signal for protein sorting into the multivesicular body pathway, J Cell Biol, 185, 493, 10.1083/jcb.200810114
Song, 2010, The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome, Genes Dev, 24, 10.1101/gad.1925010
Spence, 2000, Cell cycle-regulated modification of the ribosome by a variant multiubiquitin chain, Cell, 102, 67, 10.1016/S0092-8674(00)00011-8
Flick, 2004, Proteolysis-independent regulation of the transcription factor Met4 by a single Lys 48-linked ubiquitin chain, Nat Cell Biol, 6, 10.1038/ncb1143
Emmerich, 2016, Lys63/Met1-hybrid ubiquitin chains are commonly formed during the activation of innate immune signalling, Biochem Biophys Res Commun, 474, 10.1016/j.bbrc.2016.04.141
Meyer, 2014, Enhanced protein degradation by branched ubiquitin chains, Cell, 157, 10.1016/j.cell.2014.03.037
Ohtake, 2018, K63 ubiquitylation triggers proteasomal degradation by seeding branched ubiquitin chains, Proc Natl Acad Sci USA, 115, 10.1073/pnas.1716673115
Liu, 2017, Ufd2p synthesizes branched ubiquitin chains to promote the degradation of substrates modified with atypical chains, Nat Commun, 8, 1, 10.1038/ncomms14274
Johnson, 1995, Proteolytic Pathway That Recognizes Ubiquitin as a Degradation Signal, J Biol Chem, 270, 10.1074/jbc.270.29.17442
Leto, 2019, Genome-wide CRISPR Analysis Identifies Substrate-Specific Conjugation Modules in ER-Associated Degradation, Mol Cell, 73, 10.1016/j.molcel.2018.11.015
Besche, 2014, Autoubiquitination of the 26S Proteasome on Rpn13 Regulates Breakdown of Ubiquitin Conjugates, EMBO J, 33, 10.1002/embj.201386906
Deol, 2020, Proteasome-Bound UCH37/UCHL5 Debranches Ubiquitin Chains to Promote Degradation, Mol Cell, 10.1016/j.molcel.2020.10.017
Yoshida, 2015, A comprehensive method for detecting ubiquitinated substrates using TR-TUBE, Proc Natl Acad Sci USA, 112, 10.1073/pnas.1422313112
Valkevich, 2014, Middle-Down mass spectrometry enables characterization of branched ubiquitin chains, Biochemistry, 53, 10.1021/bi5006305
Mevissen, 2013, OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis, Cell, 154, 10.1016/j.cell.2013.05.046
Hjerpe, 2009, Efficient protection and isolation of ubiquitylated proteins using tandem ubiquitin-binding entities, EMBO Rep, 10, 10.1038/embor.2009.192
Swatek, 2019, Insights into ubiquitin chain architecture using Ub-clipping, Nature, 572, 10.1038/s41586-019-1482-y
Bellail, 2012, A20 Ubiquitin Ligase–Mediated Polyubiquitination of RIP1 Inhibits Caspase-8 Cleavage and TRAIL-Induced Apoptosis in Glioblastoma, Cancer Discovery, 2, 10.1158/2159-8290.CD-11-0172
Venere, 2015, The mitotic kinesin KIF11 is a driver of invasion, proliferation, and self-renewal in glioblastoma, Sci Transl Med, 7, 304ra143, 10.1126/scitranslmed.aac6762
De, 2019, Hyperphosphorylation of CDH1 in glioblastoma cancer stem cells attenuates APC/CCDH1 activity and pharmacologic inhibition of APC/CCDH1/CDC20 compromises viability, Mol Cancer Res, 17, 10.1158/1541-7786.MCR-18-1361
Mao, 2015, A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells, Cell Rep, 11, 10.1016/j.celrep.2015.05.027
Wang, 2017, BIRC3 is a biomarker of mesenchymal habitat of glioblastoma, and a mediator of survival adaptation in hypoxia-driven glioblastoma habitats, Sci Rep, 7, 9350, 10.1038/s41598-017-09503-8
Liu, 2009, Human BRE1 is an E3 ubiquitin ligase for Ebp1 tumor suppressor, Mol Biol Cell, 20, 10.1091/mbc.e08-09-0983
Lee, 2018, The E3 ligase C-CBL inhibits cancer cell migration by neddylating the proto-oncogene c-Src, Oncogene, 37, 10.1038/s41388-018-0354-5
Seong, 2014, c-Cbl regulates αPix-mediated cell migration and invasion, Biochem Biophys Res Commun, 455, 10.1016/j.bbrc.2014.10.129
Hou, 2017, CSN6 controls the proliferation and metastasis of glioblastoma by CHIP-mediated degradation of EGFR, Oncogene, 36, 10.1038/onc.2016.280
Xu, 2017, The E3 ubiquitin ligase CHIP/miR-92b/PTEN regulatory network contributes to tumorigenesis of glioblastoma, Am J Cancer Res, 7, 289
Dong, 2015, Decreased CUL4B expression inhibits malignant proliferation of glioma in vitro and in vivo, Eur Rev Med Pharmacol Sci, 19
Queisser, 2014, HOIL-1L Functions as the PKCζ Ubiquitin Ligase to Promote Lung Tumor Growth, Am J Respir Crit Care Med, 190, 10.1164/rccm.201403-0463OC
Yang, 2012, Dissecting the complex regulation of Mad4 in glioblastoma multiforme cells, Cancer Biol Ther, 13, 10.4161/cbt.21814
Yang, 2014, Distinctive effects of the cellular inhibitor of apoptosis protein c-IAP2 through stabilization by XIAP in glioblastoma multiforme cells, Cell Cycle, 13, 992, 10.4161/cc.27880
Abe, 2020, LZTR1 facilitates polyubiquitination and degradation of RAS-GTPases, Cell Death Differ, 27, 10.1038/s41418-019-0395-5
Kondo, 1996, mdm2 gene mediates the expression of mdr1 gene and P-glycoprotein in a human glioblastoma cell line, Br J Cancer, 74, 10.1038/bjc.1996.527
Biernat, 1997, Amplification and Overexpression of MDM2 in Primary (de novo) Glioblastomas, J Neuropathol Exp Neurol, 56, 10.1097/00005072-199702000-00009
Joshi, 2014, MDM2 Regulates Hypoxic Hypoxia-inducible Factor 1α Stability in an E3 Ligase, Proteasome, and PTEN-Phosphatidylinositol 3-Kinase-AKT-dependent Manner, J Biol Chem, 289, 10.1074/jbc.M114.587493
Bufalieri, 2020, The RNA-binding ubiquitin ligase MEX3A affects glioblastoma tumorigenesis by inducing ubiquitylation and degradation of RIG-I, Cancers (Basel), 12, 321, 10.3390/cancers12020321
Wald, 2017, Suppression of planar cell polarity signaling and migration in glioblastoma by Nrdp1-mediated Dvl polyubiquitination, Oncogene, 36, 10.1038/onc.2017.126
Dasari, 2010, Cord Blood Stem Cell-Mediated Induction of Apoptosis in Glioma Downregulates X-Linked Inhibitor of Apoptosis Protein (XIAP), PLoS One, 5, e11813, 10.1371/journal.pone.0011813
Bunda, 2019, CIC protein instability contributes to tumorigenesis in glioblastoma, Nat Commun, 10, 661, 10.1038/s41467-018-08087-9
Shin, 2017, PRAJA is overexpressed in glioblastoma and contributes to neural precursor development, Genes Cancer, 8, 10.18632/genesandcancer.151
Lignitto, 2013, Proteolysis of MOB1 by the ubiquitin ligase praja2 attenuates Hippo signalling and supports glioblastoma growth, Nat Commun, 4, 1822, 10.1038/ncomms2791
Xie, 2019, Knockdown of RAD18 inhibits glioblastoma development, J Cell Physiol, 234, 10.1002/jcp.28713
Jia, 2009, ROC1/RBX1 E3 Ubiquitin Ligase Silencing Suppresses Tumor Cell Growth via Sequential Induction of G2-M Arrest, Apoptosis, and Senescence, Cancer Res, 69, 10.1158/0008-5472.CAN-08-4671
Wang, 2020, Downregulation of the Ubiquitin-E3 Ligase RNF123 Promotes Upregulation of the NF-κB1 Target SerpinE1 in Aggressive Glioblastoma Tumors, Cancers (Basel), 12, 1081, 10.3390/cancers12051081
Liu, 2016, RNF135, RING finger protein, promotes the proliferation of human glioblastoma cells in vivo and in vitro via the ERK pathway, Sci Rep, 6, 20642, 10.1038/srep20642
Wu, 2018, Downregulation of RNF138 inhibits cellular proliferation, migration, invasion and EMT in glioma cells via suppression of the Erk signaling pathway, Oncol Rep, 40, 10.3892/or.2018.6744
Kim, 2018, RNF138-mediated ubiquitination of rpS3 is required for resistance of glioblastoma cells to radiation-induced apoptosis, Exp Mol Med, 50, 10.1038/emm.2017.247
Jin, 2017, Targeting Glioma Stem Cells through Combined BMI1 and EZH2 Inhibition, Nat Med, 23, 10.1038/nm.4415
Du, 2019, A PRMT5-RNF168-SMURF2 Axis Controls H2AX Proteostasis, Cell Rep, 28, 3199, 10.1016/j.celrep.2019.08.031
Guardavaccaro, 2008, Control of chromosome stability by the β-TrCP-REST-Mad2 axis, Nature, 452, 10.1038/nature06641
Westbrook, 2008, SCFβ-TRCP controls oncogenic transformation and neural differentiation through REST degradation, Nature, 452, 10.1038/nature06780
Warfel, 2011, Mislocalization of the E3 Ligase, β-Transducin Repeat-containing Protein 1 (β-TrCP1), in Glioblastoma Uncouples Negative Feedback between the Pleckstrin Homology Domain Leucine-rich Repeat Protein Phosphatase 1 (PHLPP1) and Akt, J Biol Chem, 286, 10.1074/jbc.M111.237081
Zhang, 2019, TRIP13 promotes the cell proliferation, migration and invasion of glioblastoma through the FBXW7/c-MYC axis, Br J Cancer, 121, 10.1038/s41416-019-0633-0
Lin, 2018, FBW7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells, Cancer Sci, 109, 10.1111/cas.13528
Hagedorn, 2007, FBXW7/hCDC4 controls glioma cell proliferation in vitro and is a prognostic marker for survival in glioblastoma patients, Cell Div, 2, 9, 10.1186/1747-1028-2-9
Chen, 2016, Bcl-2 family member Mcl-1 expression is reduced under hypoxia by the E3 ligase FBW7 contributing to BNIP3 induced cell death in glioma cells, Cancer Biol Ther, 17, 10.1080/15384047.2015.1095399
Fang, 2017, Deubiquitinase USP13 Maintains Glioblastoma Stem Cells by Antagonizing FBXL14-mediated Myc Ubiquitination, J Exp Med, 214, 10.1084/jem.20151673
Khan, 2019, Attenuation of Tumor Suppressive Function of FBXO16 Ubiquitin Ligase Activates Wnt Signaling In Glioblastoma, Neoplasia, 21, 10.1016/j.neo.2018.11.005
Wu, 2020, Skp2 modulates proliferation, senescence and tumorigenesis of glioma, Cancer Cell Int, 20, 71, 10.1186/s12935-020-1144-z
Galeano, 2013, ADAR2-editing activity inhibits glioblastoma growth through the modulation of the CDC14B/Skp2/p21/p27 axis, Oncogene, 32, 998, 10.1038/onc.2012.125
Lee, 2014, BIS targeting induces cellular senescence through the regulation of 14-3-3 zeta/STAT3/SKP2/p27 in glioblastoma cells, Cell Death Dis, 5, e1537, 10.1038/cddis.2014.501
Mamillapalli, 2001, PTEN regulates the ubiquitin-dependent degradation of the CDK inhibitor p27KIP1 through the ubiquitin E3 ligase SCFSKP2, Curr Biol, 11, 10.1016/S0960-9822(01)00065-3
Zhang, 2018, A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis, Oncogene, 37, 10.1038/s41388-017-0019-9
He, 2019, The SIAH1–HIPK2–p53ser46 Damage Response Pathway is Involved in Temozolomide-Induced Glioblastoma Cell Death, Mol Cancer Res, 17, 10.1158/1541-7786.MCR-18-1306
Yan, 2018, CacyBP/SIP inhibits the migration and invasion behaviors of glioblastoma cells through activating Siah1 mediated ubiquitination and degradation of cytoplasmic p27, Cell Biol Int, 42, 10.1002/cbin.10889
Fortin Ensign, 2013, The Src homology 3 domain-containing guanine nucleotide exchange factor is overexpressed in high-grade gliomas and promotes tumor necrosis factor-like weak inducer of apoptosis-fibroblast growth factor-inducible 14-induced cell migration and invasion via tumor necrosis factor receptor-associated factor 2, J Biol Chem, 288, 10.1074/jbc.M113.468686
Kim, 2010, Nitric oxide induction of IRE1-α-dependent CREB phosphorylation in human glioma cells, Nitric Oxide, 23, 10.1016/j.niox.2010.04.009
Zheng, 2008, Growth Inhibition and Radiosensitization of Glioblastoma and Lung Cancer Cells by Small Interfering RNA Silencing of Tumor Necrosis Factor Receptor-Associated Factor 2, Cancer Res, 68, 10.1158/0008-5472.CAN-08-0632
Chen, 2014, Human Brat Ortholog TRIM3 Is a Tumor Suppressor That Regulates Asymmetric Cell Division in Glioblastoma, Cancer Res, 74, 10.1158/0008-5472.CAN-13-3703
Venuto, 2019, TRIM8-driven transcriptomic profile of neural stem cells identified glioma-related nodal genes and pathways, Biochim Biophys Acta - Gen Subj, 1863, 491, 10.1016/j.bbagen.2018.12.001
Zhang, 2017, TRIM8 regulates stemness in glioblastoma through PIAS3-STAT3, Mol Oncol, 11, 10.1002/1878-0261.12034
Liu, 2018, Mutual Stabilization between TRIM9 Short Isoform and MKK6 Potentiates p38 Signaling to Synergistically Suppress Glioblastoma Progression, Cell Rep, 23, 10.1016/j.celrep.2018.03.096
Di, 2013, TRIM11 is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth, Oncogene, 32, 10.1038/onc.2012.531
Feng, 2019, Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells, J Exp Clin Cancer Res, 38, 57, 10.1186/s13046-019-1070-x
Xue, 2015, Tumour suppressor TRIM33 targets nuclear β-catenin degradation, Nat Commun, 6, 6156, 10.1038/ncomms7156
Zhang, 2017, TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination, Cell Death Dis, 8, 10.1038/cddis.2017.149
Zhang, 2014, MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab, Mol Cancer, 13, 63, 10.1186/1476-4598-13-63
Xiao, 2016, MicroRNA-566 modulates vascular endothelial growth factor by targeting Von Hippel-Landau in human glioblastoma in vitro and in vivo, Mol Med Rep, 13, 10.3892/mmr.2015.4537
Kanno, 2013, The VHL tumor suppressor protein regulates tumorigenicity of U87-derived glioma stem-like cells by inhibiting the JAK/STAT signaling pathway, Int J Oncol, 42, 10.3892/ijo.2013.1773
Wang, 2017, PARK2 negatively regulates the metastasis and epithelial-mesenchymal transition of glioblastoma cells via ZEB1, Oncol Lett, 14, 10.3892/ol.2017.6488
Scott, 2017, Polyubiquitination of apurinic/apyrimidinic endonuclease 1 by Parkin, Mol Carcinog, 56, 10.1002/mc.22495
Oikonomaki, 2017, Ubiquitin Specific Peptidase 15 (USP15) suppresses glioblastoma cell growth via stabilization of HECTD1 E3 ligase attenuating WNT pathway activity, Oncotarget, 8, 10.18632/oncotarget.22798
Li, 2019, HERC3-Mediated SMAD7 ubiquitination degradation promotes autophagy-induced EMT and chemoresistance in Glioblastoma, Clin Cancer Res, 25, 10.1158/1078-0432.CCR-18-3791
Zhao, 2009, The N-Myc-DLL3 Cascade Is Suppressed by the Ubiquitin Ligase Huwe1 to Inhibit Proliferation and Promote Neurogenesis in the Developing Brain, Dev Cell, 17, 10.1016/j.devcel.2009.07.009
Su, 2019, Meta-analysis of gene expression alterations and clinical significance of the HECT domain-containing ubiquitin ligase HUWE1 in cancer, Oncol Lett, 18, 10.3892/ol.2019.10579
Panner, 2009, A Novel PTEN-dependent Link to Ubiquitination Controls FLIPS Stability and TRAIL Sensitivity in Glioblastoma Multiforme, Cancer Res, 69, 10.1158/0008-5472.CAN-09-1287
Dai, 2010, FoxM1B Regulates NEDD4-1 Expression, Leading to Cellular Transformation and Full Malignant Phenotype in Immortalized Human Astrocytes, Cancer Res, 70, 10.1158/0008-5472.CAN-09-3909
Chang, 2018, Suppression of the Smurf1 Expression Inhibits Tumor Progression in Gliomas, Cell Mol Neurobiol, 38, 10.1007/s10571-017-0485-1
Eichhorn, 2012, USP15 stabilizes TGF-β receptor I and promotes oncogenesis through the activation of TGF-β signaling in glioblastoma, Nat Med, 18, 10.1038/nm.2619
Braganza, 2017, UBE3B is a calmodulin-regulated, mitochondrion-associated E3 ubiquitin ligase, J Biol Chem, 292, 10.1074/jbc.M116.766824
Svilar, 2012, Alkylation sensitivity screens reveal a conserved cross-species functionome, Mol Cancer Res, 10, 10.1158/1541-7786.MCR-12-0168
Pan, 2015, Ubiquitin-protein Ligase E3C Promotes Glioma Progression by Mediating the Ubiquitination and Degrading of Annexin A7, Sci Rep, 5, 11066, 10.1038/srep11066
Zhao, 2020, NUSAP1 potentiates chemoresistance in glioblastoma through its SAP domain to stabilize ATR, Signal Transduct Target Ther, 5, 44, 10.1038/s41392-020-0137-7
Szymura, 2020, DDX39B interacts with the pattern recognition receptor pathway to inhibit NF-κB and sensitize to alkylating chemotherapy, BMC Biol, 18, 32, 10.1186/s12915-020-0764-z
Soares, 2013, Regulation of Stress-Inducible Phosphoprotein 1 Nuclear Retention by Protein Inhibitor of Activated STAT PIAS1, Mol Cell Proteomics, 12, 10.1074/mcp.M113.031005
Rahme, 2016, PDGF engages an E2F-USP1 signaling pathway to support ID2-mediated survival of proneural glioma cells, Cancer Res, 76, 10.1158/0008-5472.CAN-15-2157
Lee, 2016, USP1 targeting impedes GBM growth by inhibiting stem cell maintenance and radioresistance, Neuro Oncol, 18, 37, 10.1093/neuonc/nov091
Ma, 2019, Aberrant activation of β-catenin signaling drives glioma tumorigenesis via USP1-mediated stabilization of EZH2, Cancer Res, 79, 72, 10.1158/0008-5472.CAN-18-1304
Wang, 2014, Ubiquitin-specific protease 2a stabilizes MDM4 and facilitates the p53-mediated intrinsic apoptotic pathway in glioblastoma, Carcinogenesis, 35, 10.1093/carcin/bgu015
Tu, 2020, Smoothened Promotes Glioblastoma Radiation Resistance Via Activating USP3-Mediated Claspin Deubiquitination, Clin Cancer Res, 26, 10.1158/1078-0432.CCR-19-1515
Fan, 2019, Ubiquitin-specific protease 3 promotes glioblastoma cell invasion and epithelial-mesenchymal transition via stabilizing snail, Mol Cancer Res, 17, 10.1158/1541-7786.MCR-19-0197
Qin, 2019, Deubiquitinating enzyme 4 facilitates chemoresistance in glioblastoma by inhibiting P53 activity, Oncol Lett, 17, 10.3892/ol.2018.9654
Zhou, 2019, Ubiquitin-specific protease 4 promotes glioblastoma multiforme via activating ERK pathway, Onco Targets Ther, 12, 10.2147/OTT.S176582
Izaguirre, 2012, PTBP1-dependent regulation of USP5 alternative RNA splicing plays a role in glioblastoma tumorigenesis, Mol Carcinog, 51, 895, 10.1002/mc.20859
Huang, 2011, Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cells, Nat Cell Biol, 13, 10.1038/ncb2153
Yi, 2016, Stabilization of LSD1 by deubiquitinating enzyme USP7 promotes glioblastoma cell tumorigenesis and metastasis through suppression of the p53 signaling pathway, Oncol Rep, 36, 10.3892/or.2016.5099
Panner, 2010, Ubiquitin-specific protease 8 links the PTEN-Akt-AIP4 pathway to the control of FLIPS stability and TRAIL sensitivity in glioblastoma multiforme, Cancer Res, 70, 10.1158/0008-5472.CAN-09-3979
MacLeod, 2019, Genome-Wide CRISPR-Cas9 Screens Expose Genetic Vulnerabilities and Mechanisms of Temozolomide Sensitivity in Glioblastoma Stem Cells, Cell Rep, 27, 10.1016/j.celrep.2019.03.047
Cox, 2013, The SOX2-Interactome in Brain Cancer Cells Identifies the Requirement of MSI2 and USP9X for the Growth of Brain Tumor Cells, PLoS One, 8, e62857, 10.1371/journal.pone.0062857
Wolfsperger, 2016, Deubiquitylating enzyme USP9x regulates radiosensitivity in glioblastoma cells by Mcl-1-dependent and -independent mechanisms, Cell Death Dis, 7, e2039, 10.1038/cddis.2015.405
Karpel-Massler, 2016, Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo, Oncotarget, 7, 10.18632/oncotarget.7302
Chen, 2019, USP9X deubiquitinates ALDH1A3 and maintains mesenchymal identity in glioblastoma stem cells, J Clin Invest, 129, 10.1172/JCI126414
Grunda, 2006, Increased expression of thymidylate synthetase (TS), ubiquitin specific protease 10 (USP10) and survivin is associated with poor survival in glioblastoma multiforme (GBM), J Neurooncol, 80, 10.1007/s11060-006-9191-4
Zhao, 2020, EGFR-vIII downregulated H2AZK4/7AC though the PI3K/AKT-HDAC2 axis to regulate cell cycle progression, Clin Transl Med, 9, 10, 10.1186/s40169-020-0260-7
Wu, 2014, USP11 regulates PML stability to control Notch-induced malignancy in brain tumours, Nat Commun, 5, 3214, 10.1038/ncomms4214
Xu, 2018, Ubiquitin-specific protease 15 promotes tumor cell invasion and proliferation in glioblastoma, Oncol Lett, 15, 10.3892/ol.2018.7747
Sgorbissa, 2011, Type I IFNs signaling and apoptosis resistance in glioblastoma cells, Apoptosis, 16, 10.1007/s10495-011-0639-4
Zhou, 2016, Nuclear GSK3β promotes tumorigenesis by phosphorylating KDM1A and inducing its deubiquitylation by USP22, Nat Cell Biol, 18, 10.1038/ncb3396
Wang, 2016, Ubiquitin-specific protease 28 is overexpressed in human glioblastomas and contributes to glioma tumorigenicity by regulating MYC expression, Exp Biol Med, 241, 10.1177/1535370215595468
Zhou, 2017, Gli1-induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1, EMBO Rep, 18, 10.15252/embr.201643124
Ding, 2015, Spy1 induces de-ubiquitinating of RIP1 arrest and confers glioblastoma’s resistance to tumor necrosis factor (TNF-α)-induced apoptosis through suppressing the association of CLIPR-59 and CYLD, Cell Cycle, 14, 10.1080/15384101.2015.1041688
Guo, 2014, Hypoxia suppresses cylindromatosis (CYLD) expression to promote inflammation in glioblastoma: Possible link to acquired resistance to anti-VEGF therapy, Oncotarget, 5, 10.18632/oncotarget.2216
Hjelmeland, 2010, Targeting A20 decreases glioma stem cell survival and tumor growth, PLoS Biol, 8, e1000319, 10.1371/journal.pbio.1000319
Chai, 2014, Downregulation of BRCA1-BRCA2-containing complex subunit 3 sensitizes glioma cells to temozolomide, Oncotarget, 5, 10.18632/oncotarget.2543
Liu, 2015, EGFR Mutation Promotes Glioblastoma through Epigenome and Transcription Factor Network Remodeling, Mol Cell, 60, 10.1016/j.molcel.2015.09.002
Ermoian, 2002, Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival, Clin Cancer Res, 8
Yang, 2017, Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localization, Oncogene, 36, 10.1038/onc.2016.493
Zhou, 2003, ErbB2 degradation mediated by the co-chaperone protein CHIP, J Biol Chem, 278, 10.1074/jbc.M209640200
Cope, 2003, COP9 signalosome: A multifunctional regulator of SCF and other cullin-based ubiquitin ligases, Cell, 114, 10.1016/S0092-8674(03)00722-0
Zhao, 2011, Subunit 6 of the COP9 signalosome promotes tumorigenesis in mice through stabilization of MDM2 and is upregulated in human cancers, J Clin Invest, 121, 10.1172/JCI44111
Chen, 2014, CSN6 drives carcinogenesis by positively regulating Myc stability, Nat Commun, 5, 1, 10.1038/ncomms6384
Bruna, 2007, High TGFβ-Smad Activity Confers Poor Prognosis in Glioma Patients and Promotes Cell Proliferation Depending on the Methylation of the PDGF-B Gene, Cancer Cell, 11, 10.1016/j.ccr.2006.11.023
Colak, 2017, Targeting TGF-β Signaling in Cancer, Trends Cancer, 3, 56, 10.1016/j.trecan.2016.11.008
Kavsak, 2000, Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGFβ receptor for degradation, Mol Cell, 6, 10.1016/S1097-2765(00)00134-9
Hombach-Klonisch, 2018, Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response, Pharmacol Ther, 184, 13, 10.1016/j.pharmthera.2017.10.017
Sui, 2013, Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment, Cell Death Dis, 4, e838, 10.1038/cddis.2013.350
Lu, 2015, MIR517C inhibits autophagy and the epithelialto- mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation, Autophagy, 11, 10.1080/15548627.2015.1108507
Zhang, 2007, Smad7 Antagonizes Transforming Growth Factor Signaling in the Nucleus by Interfering with Functional Smad-DNA Complex Formation, Mol Cell Biol, 27, 10.1128/MCB.01636-06
Ebisawa, 2001, Smurf1 Interacts with Transforming Growth Factor-β Type I Receptor through Smad7 and Induces Receptor Degradation, J Biol Chem, 276, 10.1074/jbc.C100008200
Yuan, 2020, Deubiquitinating enzyme USP10 promotes hepatocellular carcinoma metastasis through deubiquitinating and stabilizing Smad4 protein, Mol Oncol, 14, 197, 10.1002/1878-0261.12596
Gao, 2009, Ubiquitin Ligase Nedd4L Targets Activated Smad2/3 to Limit TGF-β Signaling, Mol Cell, 36, 10.1016/j.molcel.2009.09.043
Derynck, 2019, Specificity, versatility, and control of TGF-b family signaling, Sci Signal, 12, eaav5183, 10.1126/scisignal.aav5183
Iyappan, 2010, Turning the RING domain protein MdmX into an active ubiquitin-protein ligase, J Biol Chem, 285, 10.1074/jbc.M110.115113
Huang, 2018, MDMX acidic domain inhibits p53 DNA binding in vivo and regulates tumorigenesis, Proc Natl Acad Sci USA, 115, 10.1073/pnas.1719090115
Popowicz, 2008, Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain, Cell Cycle, 7, 10.4161/cc.6365
Linke, 2008, Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans, Cell Death Differ, 15, 10.1038/sj.cdd.4402309
Zhang, 2011, USP4 inhibits p53 through deubiquitinating and stabilizing ARF-BP1, EMBO J, 30, 10.1038/emboj.2011.125
Sato, 2015, The TRIM-FLMN protein TRIM45 directly interacts with RACK1 and negatively regulates PKC-mediated signaling pathway, Oncogene, 34, 10.1038/onc.2014.68
Shibata, 2012, TRIM45 negatively regulates NF-κB-mediated transcription and suppresses cell proliferation, Biochem Biophys Res Commun, 423, 10.1016/j.bbrc.2012.05.090
Bonnet, 1997, Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell, Nat Med, 3, 10.1038/nm0797-730
Singh, 2003, Identification of cancer stem cell in human brain tumors, Cancer Res, 63
Bao, 2006, Glioma stem cells promote radioresistance by preferential activation of the DNA damage response, Nature, 444, 10.1038/nature05236
Liu, 2006, Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma, Mol Cancer, 5, 67, 10.1186/1476-4598-5-67
Chen, 2012, A restricted cell population propagates glioblastoma growth after chemotherapy, Nature, 488, 10.1038/nature11287
Joo, 2013, Patient-Specific Orthotopic Glioblastoma Xenograft Models Recapitulate the Histopathology and Biology of Human Glioblastomas In Situ, Cell Rep, 3, 10.1016/j.celrep.2012.12.013
Lan, 2017, Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy, Nature, 549, 10.1038/nature23666
Safa, 2015, Glioblastoma stem cells (GSCs) epigenetic plasticity and interconversion between differentiated non-GSCs and GSCs, Genes Dis, 2, 10.1016/j.gendis.2015.02.001
Dirkse, 2019, Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment, Nat Commun, 10, 1787, 10.1038/s41467-019-09853-z
Chaffer, 2011, Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state, Proc Natl Acad Sci USA, 108, 10.1073/pnas.1102454108
Popov, 2007, The ubiquitin-specific protease USP28 is required for MYC stability, Nat Cell Biol, 9, 10.1038/ncb1601
Harris, 2011, Brat Promotes Stem Cell Differentiation via Control of a Bistable Switch that Restricts BMP Signaling, Dev Cell, 20, 72, 10.1016/j.devcel.2010.11.019
Ballas, 2005, REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis, Cell, 121, 10.1016/j.cell.2005.03.013
Fuchs, 2004, The many faces of β-TrCP E3 ubiquitin ligases: Reflections in the magic mirror of cancer, Oncogene, 23, 10.1038/sj.onc.1207389
Lee, 2016, WNT signaling in glioblastoma and therapeutic opportunities, Lab Invest, 96, 10.1038/labinvest.2015.140
Carruthers, 2018, Replication stress drives constitutive activation of the DNA damage response and radioresistance in glioblastoma stem-like cells, Cancer Res, 78, 10.1158/0008-5472.CAN-18-0569
Zhang, 2009, Targeting cancer with small molecule kinase inhibitors, Nat Rev Cancer, 9, 28, 10.1038/nrc2559
Goldstein, 2008, High-throughput kinase profiling as a platform for drug discovery, Nat Rev Drug Discov, 7, 10.1038/nrd2541
Kisselev, 2001, Proteasome inhibitors: from research tools to drug candidates, Chem Biol, 8, 10.1016/S1074-5521(01)00056-4
Rock, 1994, Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules, Cell, 78, 10.1016/S0092-8674(94)90462-6
Groll, 1997, Structure of 20S proteasome from yeast at 2.4Å resolution, Nature, 386, 10.1038/386463a0
Löwe, 1995, Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution, Science, 268, 10.1126/science.7725097
Seemuller, 1995, Proteasome from Thermoplasma acidophilum: a threonine protease, Science, 268, 10.1126/science.7725107
Adams, 1999, Proteasome inhibitors: a novel class of potent and effective antitumor agents, Cancer Res, 59
Hideshima, 2003, Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341, Blood, 101, 10.1182/blood-2002-08-2543
Ma, 2003, The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents, Clin Cancer Res, 9
Orlowski, 2002, Phase I Trial of the Proteasome Inhibitor PS-341 in Patients With Refractory Hematologic Malignancies, J Clin Oncol, 20, 10.1200/JCO.2002.01.133
Aghajanian, 2002, A phase I trial of the novel proteasome inhibitor PS341 in advanced solid tumor malignancies, Clin Cancer Res, 8
Moreau, 2016, Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma, N Engl J Med, 374, 10.1056/NEJMoa1516282
Wang, 2018, Intratumoral delivery of bortezomib: Impact on survival in an intracranial glioma tumor model, J Neurosurg, 128, 695, 10.3171/2016.11.JNS161212
Ventola, 2017, Progress in nanomedicine: Approved and investigational nanodrugs, Pharmacol Ther, 42
Unsoy, 2014, Chitosan magnetic nanoparticles for pH responsive Bortezomib release in cancer therapy, BioMed Pharmacother, 68, 10.1016/j.biopha.2014.04.003
Hu, 2019, Bortezomib Dendrimer Prodrug-Based Nanoparticle System, Adv Funct Mater, 29, 1807941, 10.1002/adfm.201807941
de la Puente, 2018, Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma, J Control Release, 270, 10.1016/j.jconrel.2017.11.045
Jin, 2007, Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme charging, Nature, 447, 10.1038/nature05902
Xu, 2010, The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma, Blood, 115, 10.1182/blood-2009-07-231191
Yang, 2007, Inhibitors of Ubiquitin-Activating Enzyme (E1), a New Class of Potential Cancer Therapeutics, Cancer Res, 67, 10.1158/0008-5472.CAN-07-0568
Soucy, 2009, An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer, Nature, 458, 10.1038/nature07884
Brownell, 2010, Substrate-Assisted Inhibition of Ubiquitin-like Protein-Activating Enzymes: The NEDD8 E1 Inhibitor MLN4924 Forms a NEDD8-AMP Mimetic In Situ, Mol Cell, 37, 10.1016/j.molcel.2009.12.024
Ceccarelli, 2011, An Allosteric Inhibitor of the Human Cdc34 Ubiquitin-Conjugating Enzyme, Cell, 145, 10.1016/j.cell.2011.05.039
Strickson, 2013, The anti-inflammatory drug BAY 11-7082 suppresses the MyD88-dependent signalling network by targeting the ubiquitin system, Biochem J, 451, 10.1042/BJ20121651
Pulvino, 2012, Inhibition of proliferation and survival of diffuse large B-cell lymphoma cells by a small-molecule inhibitor of the ubiquitin-conjugating enzyme Ubc13-Uev1A, Blood, 120, 10.1182/blood-2012-02-406074
Souers, 2013, ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets, Nat Med, 19, 10.1038/nm.3048
Birkinshaw, 2019, Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutations, Nat Commun, 10, 1, 10.1038/s41467-019-10363-1
Oltersdorf, 2005, An inhibitor of Bcl-2 family proteins induces regression of solid tumours, Nature, 435, 10.1038/nature03579
Wu, 2012, Specific small molecule inhibitors of skp2-mediated p27 degradation, Chem Biol, 19, 10.1016/j.chembiol.2012.09.015
Chan, 2013, Pharmacological Inactivation of Skp2 SCF Ubiquitin Ligase Restricts Cancer Stem Cell Traits and Cancer Progression, Cell, 154, 10.1016/j.cell.2013.06.048
Kussie, 1996, Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain, Science, 274, 10.1126/science.274.5289.948
Vassilev, 2004, In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2, Science, 303, 10.1126/science.1092472
Lukashchuk, 2007, Ubiquitination and Degradation of Mutant p53, Mol Cell Biol, 27, 10.1128/MCB.00050-07
Her, 2018, Potent effect of the MDM2 inhibitor AMG232 on suppression of glioblastoma stem cells, Cell Death Dis, 9, 792, 10.1038/s41419-018-0825-1
Burgess, 2016, Clinical Overview of MDM2/X-Targeted Therapies, Front Oncol, 6, 10.3389/fonc.2016.00007
Derakhshan, 2017, Therapeutic small molecules target inhibitor of apoptosis proteins in cancers with deregulation of extrinsic and intrinsic cell death pathways, Clin Cancer Res, 23, 10.1158/1078-0432.CCR-16-2172
Birnbaum, 1994, An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs, J Virol, 68, 10.1128/JVI.68.4.2521-2528.1994
Silke, 2013, Inhibitor of Apoptosis (IAP) Proteins–Modulators of Cell Death and Inflammation, Cold Spring Harb Perspect Biol, 5, a008730, 10.1101/cshperspect.a008730
Verhagen, 2000, Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins, Cell, 102, 43, 10.1016/S0092-8674(00)00009-X
Du, 2000, Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition, Cell, 102, 33, 10.1016/S0092-8674(00)00008-8
Varfolomeev, 2007, IAP Antagonists Induce Autoubiquitination of c-IAPs, NF-κB Activation, and TNFα-Dependent Apoptosis, Cell, 131, 10.1016/j.cell.2007.10.030
Dueber, 2011, Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination, Science, 334, 10.1126/science.1207862
Sakamoto, 2001, Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation, Proc Natl Acad Sci USA, 98, 10.1073/pnas.141230798
Neklesa, 2011, Small-molecule hydrophobic tagging–induced degradation of HaloTag fusion proteins, Nat Chem Biol, 7, 10.1038/nchembio.597
Takahashi, 2019, AUTACs: Cargo-Specific Degraders Using Selective Autophagy, Mol Cell, 76, 797, 10.1016/j.molcel.2019.09.009
Simonetta, 2019, Prospective discovery of small molecule enhancers of an E3 ligase-substrate interaction, Nat Commun, 10, 1402, 10.1038/s41467-019-09358-9
Sheard, 2010, Jasmonate perception by inositol-phosphate-potentiated COI1–JAZ co-receptor, Nature, 468, 10.1038/nature09430
Gray, 2001, Auxin regulates SCFTIR1-dependent degradation of AUX/IAA proteins, Nature, 414, 10.1038/35104500
Lu, 2014, The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins, Science, 343, 10.1126/science.1244917
Kronke, 2014, Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells, Science, 343, 10.1126/science.1244851
Nero, 2014, Oncogenic protein interfaces: small molecules, big challenges, Nat Rev Cancer, 14, 10.1038/nrc3690
Słabicki, 2020, The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K, Nature, 585, 10.1038/s41586-020-2374-x
Mayor-Ruiz, 2020, Rational discovery of molecular glue degraders via scalable chemical profiling, Nat Chem Biol, 16, 10.1038/s41589-020-0594-x
Wu, 2013, Over-expression of deubiquitinating enzyme USP14 in lung adenocarcinoma promotes proliferation through the accumulation of β-catenin, Int J Mol Sci, 14, 10.3390/ijms140610749
Hu, 2005, Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14, EMBO J, 24, 10.1038/sj.emboj.7600832
Xu, 2015, Phosphorylation and activation of ubiquitin-specific protease-14 by Akt regulates the ubiquitin-proteasome system, Elife, 4, e10510, 10.7554/eLife.10510
Qiu, 2006, hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37, EMBO J, 25, 10.1038/sj.emboj.7601450
Lam, 1997, Editing of ubiquitin conjugates by an isopeptidase in the 26S proteasome, Nature, 385, 10.1038/385737a0
Mazumdar, 2010, Regulation of NF-kappaB activity and inducible nitric oxide synthase by regulatory particle non-ATPase subunit 13 (Rpn13), Proc Natl Acad Sci USA, 107, 10.1073/pnas.0913495107
Wang, 2015, Synthesis and Evaluation of Derivatives of the Proteasome Deubiquitinase Inhibitor b-AP15, Chem Biol Drug Des, 86, 10.1111/cbdd.12571
D’Arcy, 2011, Inhibition of proteasome deubiquitinating activity as a new cancer therapy, Nat Med, 17, 10.1038/nm.2536
Manasanch, 2017, Proteasome inhibitors in cancer therapy, Nat Rev Clin Oncol, 14, 10.1038/nrclinonc.2016.206
Wang, 2019, USP7: Novel drug target in cancer therapy, Front Pharmacol, 10, 10.3389/fphar.2019.00427
Li, 2004, A dynamic role of HAUSP in the p53-Mdm2 pathway, Mol Cell, 13, 10.1016/S1097-2765(04)00157-1
van der Horst, 2006, FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP, Nat Cell Biol, 8, 10.1038/ncb1469
Song, 2008, The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network, Nature, 455, 10.1038/nature07290
Reverdy, 2012, Discovery of specific inhibitors of human USP7/HAUSP deubiquitinating enzyme, Chem Biol, 19, 10.1016/j.chembiol.2012.02.007
Fan, 2013, USP7 inhibitor P22077 inhibits neuroblastoma growth via inducing p53-mediated apoptosis, Cell Death Dis, 4, e867, 10.1038/cddis.2013.400
Altun, 2011, Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes, Chem Biol, 18, 10.1016/j.chembiol.2011.08.018
Schweitzer, 2007, CSN controls NF-κB by deubiquitinylation of IκBα, EMBO J, 26, 10.1038/sj.emboj.7601600
Huang, 2009, The COP9 Signalosome Mediates β-Catenin Degradation by Deneddylation and Blocks Adenomatous Polyposis coli Destruction via USP15, J Mol Biol, 391, 691, 10.1016/j.jmb.2009.06.066
Inui, 2011, USP15 is a deubiquitylating enzyme for receptor-activated SMADs, Nat Cell Biol, 13, 10.1038/ncb2346
Ward, 2018, The structure of the deubiquitinase USP15 reveals a misaligned catalytic triad and an open ubiquitin-binding channel, J Biol Chem, 293, 10.1074/jbc.RA118.003857
Chen, 2011, Selective and cell-active inhibitors of the USP1/ UAF1 deubiquitinase complex reverse cisplatin resistance in non-small cell lung cancer cells, Chem Biol, 18, 10.1016/j.chembiol.2011.08.014
Roos, 2018, EGFRvIII–Stat5 signaling enhances glioblastoma cell migration and survival, Mol Cancer Res, 16, 10.1158/1541-7786.MCR-18-0125
Banik, 2020, Lysosome-targeting chimaeras for degradation of extracellular proteins, Nature, 584, 10.1038/s41586-020-2545-9
Griffith, 1997, Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicin, Chem Biol, 4, 10.1016/S1074-5521(97)90198-8
Sakamoto, 2003, Development of Protacs to Target Cancer-promoting Proteins for Ubiquitination and Degradation, Mol Cell Proteomics, 2, 10.1074/mcp.T300009-MCP200
Schneekloth, 2004, Chemical Genetic Control of Protein Levels: Selective in Vivo Targeted Degradation, J Am Chem Soc, 126, 10.1021/ja039025z
Winter, 2015, Phthalimide conjugation as a strategy for in vivo target protein degradation, Science, 348, 10.1126/science.aab1433
Lu, 2015, Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4, Chem Biol, 22, 10.1016/j.chembiol.2015.05.009
Buckley, 2015, HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins, ACS Chem Biol, 10, 10.1021/acschembio.5b00442
Bondeson, 2015, Catalytic in vivo protein knockdown by small-molecule PROTACs, Nat Chem Biol, 11, 10.1038/nchembio.1858
Schneekloth, 2008, Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics, Bioorg Med Chem Lett, 18, 10.1016/j.bmcl.2008.07.114
Itoh, 2010, Protein knockdown using methyl bestatin-ligand hybrid molecules: Design and synthesis of inducers of ubiquitination-mediated degradation of cellular retinoic acid-binding proteins, J Am Chem Soc, 132, 10.1021/ja100691p
Buckley, 2012, Targeting the von Hippel-Lindau E3 ubiquitin ligase using small molecules to disrupt the VHL/HIF-1α interaction, J Am Chem Soc, 134, 10.1021/ja209924v
Fischer, 2014, Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide, Nature, 512, 49, 10.1038/nature13527
Chamberlain, 2014, Structure of the human Cereblon–DDB1–lenalidomide complex reveals basis for responsiveness to thalidomide analogs, Nat Struct Mol Biol, 21, 10.1038/nsmb.2874
McClellan, 2005, Protein quality control: chaperones culling corrupt conformations, Nat Cell Biol, 7, 10.1038/ncb0805-736
Xie, 2014, Pharmacological targeting of the pseudokinase Her3, Nat Chem Biol, 10, 10.1038/nchembio.1658
Zhou, 2018, Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression, J Med Chem, 61, 10.1021/acs.jmedchem.6b01816
Qin, 2018, Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression, J Med Chem, 61, 10.1021/acs.jmedchem.8b00506
Sun, 2019, A chemical approach for global protein knockdown from mice to non-human primates, Cell Discov, 5, 10, 10.1038/s41421-018-0079-1
Brand, 2019, Homolog-Selective Degradation as a Strategy to Probe the Function of CDK6 in AML, Cell Chem Biol, 26, 300, 10.1016/j.chembiol.2018.11.006
Jiang, 2019, Development of Dual and Selective Degraders of Cyclin-Dependent Kinases 4 and 6, Angew Chemie Int Ed, 58, 10.1002/anie.201901336
Burslem, 2018, The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study, Cell Chem Biol, 25, 67, 10.1016/j.chembiol.2017.09.009
Lebraud, 2016, Protein degradation by in-cell self-assembly of proteolysis targeting chimeras, ACS Cent Sci, 2, 10.1021/acscentsci.6b00280
Liu, 2020, Light-induced control of protein destruction by opto-PROTAC, Sci Adv, 6, eaay5154, 10.1126/sciadv.aay5154
Banks, 2016, From blood-brain barrier to blood-brain interface: New opportunities for CNS drug delivery, Nat Rev Drug Discov, 15, 10.1038/nrd.2015.21