JAB1/CSN5: a new player in cell cycle control and cancer

Springer Science and Business Media LLC - Tập 5 - Trang 1-14 - 2010
Terry J Shackleford1, Francois X Claret1
1Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, USA

Tóm tắt

c-Jun activation domain-binding protein-1 (Jab1) acts as a modulator of intracellular signaling and affects cellular proliferation and apoptosis, through its existence as a monomer or as the fifth component of the constitutive photomorphogenic-9 signalosome (CSN5). Jab1/ CSN5 is involved in transcription factor specificity, deneddylation of NEDD8, and nuclear-to-cytoplasmic shuttling of key molecules. Jab1/CSN5 activities positively and negatively affect a number of pathways, including integrin signaling, cell cycle control, and apoptosis. Also, more recent studies have demonstrated the intriguing roles of Jab1/CSN5 in regulating genomic instability and DNA repair. The effects of Jab1/CSN5's multiple protein interactions are generally oncogenic in nature, and overexpression of Jab1/CSN5 in cancer provides evidence that it is involved in the tumorigenic process. In this review, we highlight our current knowledge of Jab1/CSN5 function and the recent discoveries in dissecting the Jab1 signaling pathway. Further, we also discuss the regulation of Jab1/CSN5 in cancers and its potential as a therapeutic target.

Tài liệu tham khảo

Claret FX, Hibi M, Dhut S, Toda T, Karin M: A new group of conserved coactivators that increase the specificity of AP-1 transcription factors. Nature 1996, 383: 453–457. 10.1038/383453a0 Schwechheimer C, Deng XW: COP9 signalosome revisited: a novel mediator of protein degradation. Trends Cell Biol 2001, 11: 420–426. 10.1016/S0962-8924(01)02091-8 Chamovitz DA, Segal D: JAB1/CSN5 and the COP9 signalosome. A complex situation. EMBO Rep 2001, 2: 96–101. 10.1093/embo-reports/kve028 Cope G, Suh GS, Aravind L, Schwarz SE, Zipursky SL, Koonin EV, Deshaies RJ: Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1. Science 2002, 298: 608–611. 10.1126/science.1075901 Bech-Otschir D, Kraft R, Huang X, Henklein P, Kapelari B, Pollmann C, Dubiel W: COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. Embo J 2001, 20: 1630–1639. 10.1093/emboj/20.7.1630 Oh W, Lee EW, Sung YH, Yang MR, Ghim J, Lee HW, Song J: Jab1 induces the cytoplasmic localization and degradation of p53 in coordination with Hdm2. J Biol Chem 2006, 281: 17457–17465. 10.1074/jbc.M601857200 Wan M, Cao X, Wu Y, Bai S, Wu L, Shi X, Wang N: Jab1 antagonizes TGF-beta signaling by inducing Smad4 degradation. EMBO Rep 2002, 3: 171–176. 10.1093/embo-reports/kvf024 Tomoda K, Kubota Y, Arata Y, Mori S, Maeda M, Tanaka T, Yoshida M, Yoneda-Kato N, Kato J: The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex. J Biol Chem 2002, 277: 2302–2310. 10.1074/jbc.M104431200 Bae MK, Ahn MY, Jeong JW, Bae MH, Lee YM, Bae SK, Park JW, Kim KR, Kim KW: Jab1 interacts directly with HIF-1alpha and regulates its stability. J Biol Chem 2002, 277: 9–12. 10.1074/jbc.C100442200 Adler AS, Lin M, Horlings H, Nuyten DS, van de Vijver MJ, Chang HY: Genetic regulators of large-scale transcriptional signatures in cancer. Nat Genet 2006, 38: 421–430. 10.1038/ng1752 Kwok SF, Solano R, Tsuge T, Chamovitz DA, Ecker JR, Matsui M, Deng XW: Arabidopsis homologs of a c-Jun coactivator are present both in monomeric form and in the COP9 complex, and their abundance is differentially affected by the pleiotropic cop/det/fus mutations. Plant Cell 1998, 10: 1779–1790. 10.1105/tpc.10.11.1779 Kwok SF, Staub JM, Deng XW: Characterization of two subunits of Arabidopsis 19S proteasome regulatory complex and its possible interaction with the COP9 complex. J Mol Biol 1999, 285: 85–95. 10.1006/jmbi.1998.2315 Wei N, Tsuge T, Serino G, Dohmae N, Takio K, Matsui M, Deng XW: The COP9 complex is conserved between plants and mammals and is related to the 26S proteasome regulatory complex. Curr Biol 1998, 8: 919–922. 10.1016/S0960-9822(07)00372-7 Seeger M, Kraft R, Ferrell K, Bech-Otschir D, Dumdey R, Schade R, Gordon C, Naumann M, Dubiel W: A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. Faseb J 1998, 12: 469–478. Wei N, Deng XW: Making sense of the COP9 signalsome: a regulatory protein complex conserved from Arabidopsis to human. Trends Genet 1999, 15: 98–103. 10.1016/S0168-9525(98)01670-9 Deng XW, Dubiel W, Wei N, Hofmann K, Mundt K, Colicelli J, Kato J, Naumann M, Segal D, Seeger M, Carr A, Glickman M, Chamovitz DA: Unified nomenclature for the COP9 signalosome and its subunits: an essential regulator of development. Trends Genet 2000, 16: 202–203. 10.1016/S0168-9525(00)01982-X Fukumoto A, Tomoda K, Kubota M, Kato JY, Yoneda-Kato N: Small Jab1-containing subcomplex is regulated in an anchorage- and cell cycle-dependent manner, which is abrogated by ras transformation. FEBS Lett 2005, 579: 1047–1054. 10.1016/j.febslet.2004.12.076 Oron E, Mannervik M, Rencus S, Harari-Steinberg O, Neuman-Silberberg S, Segal D, Chamovitz DA: COP9 signalosome subunits 4 and 5 regulate multiple pleiotropic pathways in Drosophila melanogaster. Development 2002, 129: 4399–4409. Bounpheng MA, Melnikova IN, Dodds SG, Chen H, Copeland NG, Gilbert DJ, Jenkins NA, Christy BA: Characterization of the mouse JAB1 cDNA and protein. Gene 2000, 242: 41–50. 10.1016/S0378-1119(99)00525-9 Wei N, Serino G, Deng XW: The COP9 signalosome: more than a protease. Trends Biochem Sci 2008, 33: 592–600. 10.1016/j.tibs.2008.09.004 Adler AS, Littlepage LE, Lin M, Kawahara TL, Wong DJ, Werb Z, Chang HY: CSN5 isopeptidase activity links COP9 signalosome activation to breast cancer progression. Cancer Res 2008, 68: 506–515. 10.1158/0008-5472.CAN-07-3060 Hallstrom TC, Nevins JR: Jab1 is a specificity factor for E2F1-induced apoptosis. Genes Dev 2006, 20: 613–623. 10.1101/gad.1345006 Cope GA, Deshaies RJ: COP9 signalosome: a multifunctional regulator of SCF and other cullin-based ubiquitin ligases. Cell 2003, 114: 663–671. 10.1016/S0092-8674(03)00722-0 Chamovitz DA: Revisiting the COP9 signalosome as a transcriptional regulator. EMBO Rep 2009, 10: 352–358. 10.1038/embor.2009.33 Kato JY, Yoneda-Kato N: Mammalian COP9 signalosome. Genes Cells 2009, 14: 1209–1225. 10.1111/j.1365-2443.2009.01349.x Wei N, Deng XW: The COP9 signalosome. Annu Rev Cell Dev Biol 2003, 19: 261–286. 10.1146/annurev.cellbio.19.111301.112449 Wolf DA, Zhou C, Wee S: The COP9 signalosome: an assembly and maintenance platform for cullin ubiquitin ligases? Nat Cell Biol 2003, 5: 1029–1033. 10.1038/ncb1203-1029 Dubiel W: Resolving the CSN and CAND1 paradoxes. Mol Cell 2009, 35: 547–549. 10.1016/j.molcel.2009.08.011 Maytal-Kivity V, Reis N, Hofmann K, Glickman MH: MPN+, a putative catalytic motif found in a subset of MPN domain proteins from eukaryotes and prokaryotes, is critical for Rpn11 function. BMC Biochem 2002, 3: 28. 10.1186/1471-2091-3-28 Verma R, Aravind L, Oania R, McDonald WH, Yates JR, Koonin EV, Deshaies RJ: Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science 2002, 298: 611–615. 10.1126/science.1075898 Liu Y, Shah SV, Xiang X, Wang J, Deng ZB, Liu C, Zhang L, Wu J, Edmonds T, Jambor C, Kappes JC, Zhang HG: COP9-associated CSN5 regulates exosomal protein deubiquitination and sorting. Am J Pathol 2009, 174: 1415–1425. 10.2353/ajpath.2009.080861 Shaulian E, Karin M: AP-1 in cell proliferation and survival. Oncogene 2001, 20: 2390–2400. 10.1038/sj.onc.1204383 Jochum W, Passegue E, Wagner EF: AP-1 in mouse development and tumorigenesis. Oncogene 2001, 20: 2401–2412. 10.1038/sj.onc.1204389 Vogt PK: Jun, the oncoprotein. Oncogene 2001, 20: 2365–2377. 10.1038/sj.onc.1204443 Eferl R, Wagner EF: AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer 2003, 3: 859–868. 10.1038/nrc1209 Bianchi E, Denti S, Granata A, Bossi G, Geginat J, Villa A, Rogge L, Pardi R: Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity. Nature 2000, 404: 617–621. 10.1038/35007098 Chauchereau A, Georgiakaki M, Perrin-Wolff M, Milgrom E, Loosfelt H: JAB1 interacts with both the progesterone receptor and SRC-1. J Biol Chem 2000, 275: 8540–8548. 10.1074/jbc.275.12.8540 Li S, Liu X, Ascoli M: p38JAB1 binds to the intracellular precursor of the lutropin/choriogonadotropin receptor and promotes its degradation. J Biol Chem 2000, 275: 13386–13393. 10.1074/jbc.275.18.13386 Levinson H, Sil AK, Conwell JE, Hopper JE, Ehrlich HP: Alpha V integrin prolongs collagenase production through Jun activation binding protein 1. Ann Plast Surg 2004, 53: 155–161. 10.1097/01.sap.0000112281.97409.a6 Kleemann R, Hausser A, Geiger G, Mischke R, Burger-Kentischer A, Flieger O, Johannes FJ, Roger T, Calandra T, Kapurniotu A, Grell M, Finkelmeier D, Brunner H, Bernhagen J: Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1. Nature 2000, 408: 211–216. 10.1038/35041591 Lu C, Li Y, Zhao Y, Xing G, Tang F, Wang Q, Sun Y, Wei H, Yang X, Wu C, Chen J, Guan KL, Zhang C, Chen H, He F: Intracrine hepatopoietin potentiates AP-1 activity through JAB1 independent of MAPK pathway. Faseb J 2002, 16: 90–92. Tanaka Y, Kanai F, Ichimura T, Tateishi K, Asaoka Y, Guleng B, Jazag A, Ohta M, Imamura J, Ikenoue T, Ijichi H, Kawabe T, Isobe T, Omata M: The hepatitis B virus X protein enhances AP-1 activation through interaction with Jab1. Oncogene 2006, 25: 633–642. 10.1038/sj.onc.1209311 Lopez-Bergami P, Lau E, Ronai Z: Emerging roles of ATF2 and the dynamic AP1 network in cancer. Nat Rev Cancer 2010, 10: 65–76. 10.1038/nrc2681 Gee JM, Barroso AF, Ellis IO, Robertson JF, Nicholson RI: Biological and clinical associations of c-jun activation in human breast cancer. Int J Cancer 2000, 89: 177–186. 10.1002/(SICI)1097-0215(20000320)89:2<177::AID-IJC13>3.0.CO;2-0 Yokoyama Y, Sagara M, Sato S, Saito Y: Value of glutathione S-transferase pi and the oncogene products c-Jun, c-Fos, c-H-Ras, and c-Myc as a prognostic indicator in endometrial carcinomas. Gynecol Oncol 1998, 68: 280–287. 10.1006/gyno.1998.4936 Tiniakos DG, Scott LE, Corbett IP, Piggott NH, Horne CH: Studies of c-jun oncogene expression in human breast using a new monoclonal antibody, NCL-DK4. J Pathol 1994, 172: 19–26. 10.1002/path.1711720106 Dechend R, Hirano F, Lehmann K, Heissmeyer V, Ansieau S, Wulczyn FG, Scheidereit C, Leutz A: The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators. Oncogene 1999, 18: 3316–3323. 10.1038/sj.onc.1202717 Kwak HJ, Kim SH, Yoo HG, Park SH, Lee CH: Jun activation domain-binding protein 1 is required for mitotic checkpoint activation via its involvement in hyperphosphorylation of 53BP1. J Cancer Res Clin Oncol 2005, 131: 789–796. 10.1007/s00432-005-0035-y Huang YT, Iwamoto K, Kurosaki T, Nasu M, Ueda S: The neuronal POU transcription factor Brn-2 interacts with Jab1, a gene involved in the onset of neurodegenerative diseases. Neurosci Lett 2005, 382: 175–178. 10.1016/j.neulet.2005.03.008 Dai YS, Hao J, Bonin C, Morikawa Y, Cserjesi P: JAB1 enhances HAND2 transcriptional activity by regulating HAND2 DNA binding. J Neurosci Res 2004, 76: 613–622. 10.1002/jnr.20105 Sun Y, Wilson MP, Majerus PW: Inositol 1,3,4-trisphosphate 5/6-kinase associates with the COP9 signalosome by binding to CSN1. J Biol Chem 2002, 277: 45759–45764. 10.1074/jbc.M208709200 Uhle S, Medalia O, Waldron R, Dumdey R, Henklein P, Bech-Otschir D, Huang X, Berse M, Sperling J, Schade R, Dubiel W: Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. Embo J 2003, 22: 1302–1312. 10.1093/emboj/cdg127 Tomoda K, Kubota Y, Kato J: Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by Jab1. Nature 1999, 398: 160–165. 10.1038/18230 Toyoshima H, Hunter T: p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell 1994, 78: 67–74. 10.1016/0092-8674(94)90573-8 Polyak K, Lee MH, Erdjument-Bromage H, Koff A, Roberts JM, Tempst P, Massague J: Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 1994, 78: 59–66. 10.1016/0092-8674(94)90572-X Fero ML, Randel E, Gurley KE, Roberts JM, Kemp CJ: The murine gene p27Kip1 is haplo-insufficient for tumor suppression. Nature 1998, 396: 177–180. 10.1038/24179 Loda M, Cukor B, Tam SW, Lavin P, Fiorentino M, Draetta GF, Jessup JM, Pagano M: Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat Med 1997, 3: 231–234. 10.1038/nm0297-231 Guo Y, Sklar GN, Borkowski A, Kyprianou N: Loss of the cyclin-dependent kinase inhibitor p27(Kip1) protein in human prostate cancer correlates with tumor grade. Clin Cancer Res 1997, 3: 2269–2274. Masciullo V, Sgambato A, Pacilio C, Pucci B, Ferrandina G, Palazzo J, Carbone A, Cittadini A, Mancuso S, Scambia G, Giordano A: Frequent loss of expression of the cyclin-dependent kinase inhibitor p27 in epithelial ovarian cancer. Cancer Res 1999, 59: 3790–3794. Singh SP, Lipman J, Goldman H, Ellis FH Jr, Aizenman L, Cangi MG, Signoretti S, Chiaur DS, Pagano M, Loda M: Loss or altered subcellular localization of p27 in Barrett's associated adenocarcinoma. Cancer Res 1998, 58: 1730–1735. Ciaparronne M, Yamamoto H, Yao Y, Sgambato A, Cattoretti G, Tomita N, Monden T, Rotterdam H, Weinstein IB: Localization and expression of p27KIP1 in multistage colorectal carcinogenesis. Cancer Res 1998, 58: 114–122. Larrea MD, Wander SA, Slingerland JM: p27 as Jekyll and Hyde: regulation of cell cycle and cell motility. Cell Cycle 2009, 8: 3455–3461. Bar-Sagi D, Hall A: Ras and Rho GTPases: a family reunion. Cell 2000, 103: 227–238. 10.1016/S0092-8674(00)00115-X Tian M, Schiemann WP: The TGF-beta paradox in human cancer: an update. Future Oncol 2009, 5: 259–271. 10.2217/14796694.5.2.259 Bierie B, Moses HL: Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer 2006, 6: 506–520. 10.1038/nrc1926 Massague J, Wotton D: Transcriptional control by the TGF-beta/Smad signaling system. Embo J 2000, 19: 1745–1754. 10.1093/emboj/19.8.1745 Imamura T, Takase M, Nishihara A, Oeda E, Hanai J, Kawabata M, Miyazono K: Smad6 inhibits signalling by the TGF-beta superfamily. Nature 1997, 389: 622–626. 10.1038/39355 Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE, Heldin CH, ten Dijke P: Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature 1997, 389: 631–635. 10.1038/39369 Kim BC LH, Park SH, Lee SR, Karpova TS, McNally JG, Felici A, Lee DK, Kim SJ: Jab1/CSN5, a Component of the COP9 Signalosome, Regulates Transforming Growth Factor beta Signaling by Binding to Smad7 and Promoting Its Degradation. Mol Cell Biol 2004, 24: 2251–2262. 10.1128/MCB.24.6.2251-2262.2004 Huang J, Yuan H, Lu C, Liu X, Cao X, Wan M: Jab1 mediates protein degradation of the Rad9-Rad1-Hus1 checkpoint complex. J Mol Biol 2007, 371: 514–527. 10.1016/j.jmb.2007.05.095 Tian L, Peng G, Parant JM, Leventaki V, Drakos E, Zhang Q, Parker-Thornburg J, Shackleford TJ, Dai H, Lin SY, Lozano G, Rassidakis GZ, Claret FX: Essential roles of Jab1 in cell survival, spontaneous DNA damage and DNA repair. Oncogene 2010. 10.1038/onc.2010.345 Lee JW, Bae SH, Jeong JW, Kim SH, Kim KW: Hypoxia-inducible factor (HIF-1)alpha: its protein stability and biological functions. Exp Mol Med 2004, 36: 1–12. Fejzo MS, Godfrey T, Chen C, Waldman F, Gray JW: Molecular cytogenetic analysis of consistent abnormalities at 8q12-q22 in breast cancer. Genes Chromosomes Cancer 1998, 22: 105–113. 10.1002/(SICI)1098-2264(199806)22:2<105::AID-GCC4>3.0.CO;2-0 Sun J, Liu W, Adams TS, Li X, Turner AR, Chang B, Kim JW, Zheng SL, Isaacs WB, Xu J: DNA copy number alterations in prostate cancers: a combined analysis of published CGH studies. Prostate 2007, 67: 692–700. 10.1002/pros.20543 Rummukainen J, Kytola S, Karhu R, Farnebo F, Larsson C, Isola JJ: Aberrations of chromosome 8 in 16 breast cancer cell lines by comparative genomic hybridization, fluorescence in situ hybridization, and spectral karyotyping. Cancer Genet Cytogenet 2001, 126: 1–7. 10.1016/S0165-4608(00)00387-3 Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL: Genetic alterations during colorectal-tumor development. N Engl J Med 1988, 319: 525–532. 10.1056/NEJM198809013190901 Dimova I, Orsetti B, Negre V, Rouge C, Ursule L, Lasorsa L, Dimitrov R, Doganov N, Toncheva D, Theillet C: Genomic markers for ovarian cancer at chromosomes 1, 8 and 17 revealed by array CGH analysis. Tumori 2009, 95: 357–366. Bieche I, Lidereau R: Genetic alterations in breast cancer. Genes Chromosomes Cancer 1995, 14: 227–251. 10.1002/gcc.2870140402 Emberley ED, Niu Y, Curtis L, Troup S, Mandal SK, Myers JN, Gibson SB, Murphy LC, Watson PH: The S100A7-c-Jun activation domain binding protein 1 pathway enhances prosurvival pathways in breast cancer. Cancer Res 2005, 65: 5696–5702. 10.1158/0008-5472.CAN-04-3927 Emberley ED, Niu Y, Leygue E, Tomes L, Gietz RD, Murphy LC, Watson PH: Psoriasin interacts with Jab1 and influences breast cancer progression. Cancer Res 2003, 63: 1954–1961. Hsu MC, Chang HC, Hung WC: HER-2/neu transcriptionally activates Jab1 expression via the AKT/beta-catenin pathway in breast cancer cells. Endocr Relat Cancer 2007, 14: 655–667. 10.1677/ERC-07-0077 Tomoda K, Kato JY, Tatsumi E, Takahashi T, Matsuo Y, Yoneda-Kato N: The Jab1/COP9 signalosome subcomplex is a downstream mediator of Bcr-Abl kinase activity and facilitates cell-cycle progression. Blood 2005, 105: 775–783. 10.1182/blood-2004-04-1242 Hsu MC, Huang CC, Chang HC, Hu TH, Hung WC: Overexpression of Jab1 in hepatocellular carcinoma and its inhibition by peroxisome proliferator-activated receptor{gamma} ligands in vitro and in vivo. Clin Cancer Res 2008, 14: 4045–4052. 10.1158/1078-0432.CCR-07-5040 Tomoda K, Yoneda-Kato N, Fukumoto A, Yamanaka S, Kato JY: Multiple functions of Jab1 are required for early embryonic development and growth potential in mice. J Biol Chem 2004, 279: 43013–43018. 10.1074/jbc.M406559200 Panattoni M, Sanvito F, Basso V, Doglioni C, Casorati G, Montini E, Bender JR, Mondino A, Pardi R: Targeted inactivation of the COP9 signalosome impairs multiple stages of T cell development. J Exp Med 2008, 205: 465–477. 10.1084/jem.20070725 Mori M, Yoneda-Kato N, Yoshida A, Kato JY: Stable form of JAB1 enhances proliferation and maintenance of hematopoietic progenitors. J Biol Chem 2008, 283: 29011–29021. 10.1074/jbc.M804539200 Supriatno , Harada K, Yoshida H, Sato M: Basic investigation on the development of molecular targeting therapy against cyclin-dependent kinase inhibitor p27Kip1 in head and neck cancer cells. Int J Oncol 2005, 27: 627–635. Koff A: How to decrease p27Kip1 levels during tumor development. Cancer Cell 2006, 9: 75–76. 10.1016/j.ccr.2006.01.020 Chu IM, Hengst L, Slingerland JM: The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat Rev Cancer 2008, 8: 253–267. 10.1038/nrc2347 Viglietto G, Motti ML, Bruni P, Melillo RM, D'Alessio A, Califano D, Vinci F, Chiappetta G, Tsichlis P, Bellacosa A, Fusco A, Santoro : Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. Nat Med 2002, 8: 1136–1144. 10.1038/nm762 Besson A, Gurian-West M, Chen X, Kelly-Spratt KS, Kemp CJ, Roberts JM: A pathway in quiescent cells that controls p27Kip1 stability, subcellular localization, and tumor suppression. Genes Dev 2006, 20: 47–64. 10.1101/gad.1384406 Kouvaraki MA, Tian L, Mansouri A, Zhang Q, Kumar R, Kittas C, Claret FX: Jun activation domain-binding protein 1 expression in breast cancer inversely correlates with the cell cycle inhibitor p27(Kip1). Cancer Res 2003, 63: 2977–2981. Esteva FJ, Sahin AA, Rassidakis GZ, Yuan LX, Smith TL, Yang Y, Gilcrease MZ, Cristofanilli M, Nahta R, Pusztai L, Claret FX: Jun activation domain binding protein 1 expression is associated with low p27(Kip1)levels in node-negative breast cancer. Clin Cancer Res 2003, 9: 5652–5659. Sui L, Dong Y, Watanabe Y, Yamaguchi F, Sugimoto K, Tokuda M: Clinical significance of Skp2 expression, alone and combined with Jab1 and p27 in epithelial ovarian tumors. Oncol Rep 2006, 15: 765–771. Smith LM, Wise SC, Hendricks DT, Sabichi AL, Bos T, Reddy P, Brown PH, Birrer MJ: cJun overexpression in MCF-7 breast cancer cells produces a tumorigenic, invasive and hormone resistant phenotype. Oncogene 1999, 18: 6063–6070. 10.1038/sj.onc.1202989 Ozanne BWML, Spence HJ, Johnston I, Winnie J, Meagher L, Stapleton G: Transcriptional regulation of cell invasion: AP-1 regulation of a multigenic invasion programme. Eur J Cancer 2000, 36: 1640–1648. 10.1016/S0959-8049(00)00175-1 Patil MA, Gutgemann I, Zhang J, Ho C, Cheung ST, Ginzinger D, Li R, Dykema KJ, So S, Fan ST, Kakar S, Furge KA, Buttner R, Chen X: Array-based comparative genomic hybridization reveals recurrent chromosomal aberrations and Jab1 as a potential target for 8q gain in hepatocellular carcinoma. Carcinogenesis 2005, 26: 2050–2057. 10.1093/carcin/bgi178 Wang J, Barnes RO, West NR, Olson M, Chu JE, Watson PH: Jab1 is a target of EGFR signaling in ERalpha-negative breast cancer. Breast Cancer Res 2008, 10: R51. 10.1186/bcr2105 Hsu MC, Chai CY, Hou MF, Chang HC, Chen WT, Hung WC: Jab1 is overexpressed in human breast cancer and is a downstream target for HER-2/neu. Mod Pathol 2008, 21: 609–616. 10.1038/modpathol.2008.23 Kouvaraki MA, Korapati AL, Rassidakis GZ, Tian L, Zhang Q, Chiao P, Ho L, Evans DB, Claret FX: Potential Role of Jun Activation Domain-Binding Protein 1 as a Negative Regulator of p27kip1 in Pancreatic Adenocarcinoma. Cancer Res 2006, 66: 8581–8589. 10.1158/0008-5472.CAN-06-0975 Richardson KS, Zundel W: The emerging role of the COP9 signalosome in cancer. Mol Cancer Res 2005, 3: 645–653. 10.1158/1541-7786.MCR-05-0233 Orel L, Neumeier H, Hochrainer K, Binder BR, Schmid JA: Crosstalk between the NF-kappaB activating IKK-complex and the CSN signalosome. J Cell Mol Med 2010, 14: 1555–1568. 10.1111/j.1582-4934.2009.00866.x Caballero OL, Resto V, Patturajan M, Meerzaman D, Guo MZ, Engles J, Yochem R, Ratovitski E, Sidransky D, Jen J: Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1). Oncogene 2002, 21: 3003–3010. 10.1038/sj.onc.1205390 Hwang CY, Ryu YS, Chung MS, Kim KD, Park SS, Chae SK, Chae HZ, Kwon KS: Thioredoxin modulates activator protein 1 (AP-1) activity and p27Kip1 degradation through direct interaction with Jab1. Oncogene 2004, 23: 8868–8875. 10.1038/sj.onc.1208116 Jeon JH, Lee KN, Hwang CY, Kwon KS, You KH, Choi I: Tumor suppressor VDUP1 increases p27(kip1) stability by inhibiting JAB1. Cancer Res 2005, 65: 4485–4489. 10.1158/0008-5472.CAN-04-2271 Hsieh YH, Su IJ, Wang HC, Tsai JH, Huang YJ, Chang WW, Lai MD, Lei HY, Huang W: Hepatitis B virus pre-S2 mutant surface antigen induces degradation of cyclin-dependent kinase inhibitor p27Kip1 through c-Jun activation domain-binding protein 1. Mol Cancer Res 2007, 5: 1063–1072. 10.1158/1541-7786.MCR-07-0098 Berg JP, Zhou Q, Breuhahn K, Schirmacher P, Patil MA, Chen X, Schafer N, Holler TT, Fischer HP, Buttner R, Gutgemann I: Inverse expression of Jun activation domain binding protein 1 and cell cycle inhibitor p27Kip1: influence on proliferation in hepatocellular carcinoma. Hum Pathol 2007, 38: 1621–1627. 10.1016/j.humpath.2007.03.007 Zhang XC, Chen J, Su CH, Yang HY, Lee MH: Roles for CSN5 in control of p53/MDM2 activities. J Cell Biochem 2008, 103: 1219–1230. 10.1002/jcb.21504 Callige M, Kieffer I, Richard-Foy H: CSN5/Jab1 is involved in ligand-dependent degradation of estrogen receptor {alpha} by the proteasome. Mol Cell Biol 2005, 25: 4349–4358. 10.1128/MCB.25.11.4349-4358.2005 Doronkin S, Djagaeva I, Beckendorf SK: CSN5/Jab1 mutations affect axis formation in the Drosophila oocyte by activating a meiotic checkpoint. Development 2002, 129: 5053–5064. Kim JH, Choi JK, Cinghu S, Jang JW, Lee YS, Li YH, Goh YM, Chi XZ, Lee KS, Wee H, Bae SC: Jab1/CSN5 induces the cytoplasmic localization and degradation of RUNX3. J Cell Biochem 2009, 107: 557–565. 10.1002/jcb.22157 Lue H, Thiele M, Franz J, Dahl E, Speckgens S, Leng L, Fingerle-Rowson G, Bucala R, Luscher B, Bernhagen J: Macrophage migration inhibitory factor (MIF) promotes cell survival by activation of the Akt pathway and role for CSN5/JAB1 in the control of autocrine MIF activity. Oncogene 2007, 26: 5046–5059. 10.1038/sj.onc.1210318 Yun J, Tomida A, Andoh T, Tsuruo T: Interaction between glucose-regulated destruction domain of DNA topoisomerase IIalpha and MPN domain of Jab1/CSN5. J Biol Chem 2004, 279: 31296–31303. 10.1074/jbc.M401411200 Nishimoto A, Lu L, Hayashi M, Nishiya T, Horinouchi T, Miwa S: Jab1 regulates levels of endothelin type A and B receptors by promoting ubiquitination and degradation. Biochem Biophys Res Commun 2010, 391: 1616–1622. 10.1016/j.bbrc.2009.12.087 Bemis L, Chan DA, Finkielstein CV, Qi L, Sutphin PD, Chen X, Stenmark K, Giaccia AJ, Zundel W: Distinct aerobic and hypoxic mechanisms of HIF-alpha regulation by CSN5. Genes Dev 2004, 18: 739–744. 10.1101/gad.1180104 Haag J, Aigner T: Jun activation domain-binding protein 1 binds Smad5 and inhibits bone morphogenetic protein signaling. Arthritis Rheum 2006, 54: 3878–3884. 10.1002/art.22261 Luo W, Wang Y, Hanck T, Stricker R, Reiser G: Jab1, a novel protease-activated receptor-2 (PAR-2)-interacting protein, is involved in PAR-2-induced activation of activator protein-1. J Biol Chem 2006, 281: 7927–7936. 10.1074/jbc.M510784200 Wang J, Li C, Liu Y, Mei W, Yu S, Liu C, Zhang L, Cao X, Kimberly RP, Grizzle W, Zhang HG: JAB1 determines the response of rheumatoid arthritis synovial fibroblasts to tumor necrosis factor-alpha. Am J Pathol 2006, 169: 889–902. 10.2353/ajpath.2006.051161 Bakema JE, Hiemstra IH, Bakker J, de Haij S, Kok Y, Adema G, van Egmond M, Coffer PJ, van de Winkel JG, Leusen JH: c-Jun activating binding protein 1 binds to the IgA receptor and modulates protein levels of FcalphaRI and FcRgamma-chain. Eur J Immunol 2010, 40: 2035–2040. 10.1002/eji.200939985 Yun HM, Baik JH, Kang I, Jin C, Rhim H: Physical interaction of Jab1 with human serotonin 6 G-protein-coupled receptor and their possible roles in cell survival. J Biol Chem 2010, 285: 10016–10029. 10.1074/jbc.M109.068759 Korbonits M, Chahal HS, Kaltsas G, Jordan S, Urmanova Y, Khalimova Z, Harris PE, Farrell WE, Claret FX, Grossman AB: Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors. J Clin Endocrinol Metab 2002, 87: 2635–2643. 10.1210/jc.87.6.2635 Fukumoto AIN, Sho M, Tomoda K, Kanehiro H, Hisanaga M, Tsurui Y, Tsutsumi M, Kato JY, Nakajima Y: Prognostic significance of localized p27Kip1 and potential role of Jab1/CSN5 in pancreatic cancer. Oncol Rep 2004, 11: 277–284. Harada K, Kawashima Y, Yoshida H, Sato M: High expression of Jun activation domain-binding protein 1 (Jab1) is a strong prognostic marker in oral squamous cell carcinoma patients treated by UFT in combination with radiation. Anticancer Res 2006, 26: 1615–1619. Shintani S LC, Mihara M, Hino S, Nakashiro K, Hamakawa H: Skp2 and Jab1 expression are associated with inverse expression of p27(KIP1) and poor prognosis in oral squamous cell carcinomas. Oncology 2003, 65: 355–362. 10.1159/000074649 Sui L, Dong Y, Ohno M, Watanabe Y, Sugimoto K, Tai Y, Tokuda M: Jab1 expression is associated with inverse expression of p27(kip1) and poor prognosis in epithelial overian tumors. Clin Cancer Res 2001, 7: 4130–4135. Wang Y, Cheng C, Ji Y, Zhao Y, Zou L, Shen A: Expression of Jun activation domain-binding protein 1 and Ser10 phosphorylated p27 protein in human epithelial ovarian carcinoma. J Cancer Res Clin Oncol 2009, 135: 951–959. 10.1007/s00432-008-0531-y Shen L, Tsuchida R, Miyauchi J, Saeki M, Honna T, Tsunematsu Y, Kato J, Mizutani S: Differentiation-associated expression and intracellular localization of cyclin-dependent kinase inhibitor p27KIP1 and c-Jun co-activator JAB1 in neuroblastoma. Int J Oncol 2000, 17: 749–754. Tsuchida R, Miyauchi J, Shen L, Takagi M, Tsunematsu Y, Saeki M, Honna T, Yamada S, Teraoka H, Kato JY, Mizutani S: Expression of cyclin-dependent kinase inhibitor p27/Kip1 and AP-1 coactivator p38/Jab1 correlates with differentiation of embryonal rhabdomyosarcoma. Jpn J Cancer Res 2002, 93: 1000–1006. Hashimoto N, Yachida S, Okano K, Wakabayashi H, Imaida K, Kurokohchi K, Masaki T, Kinoshita H, Tominaga M, Ajiki T, Ku Y, Okabayashi T, Hanazaki K, Hiroi M, Izumi S, Mano S, Okada S, Karasawa Y, Maeba T, Suzuki Y: Immunohistochemically detected expression of p27(Kip1) and Skp2 predicts survival in patients with intrahepatic cholangiocarcinomas. Ann Surg Oncol 2009, 16: 395–403. 10.1245/s10434-008-0236-0 Dong Y, Sui L, Watanabe Y, Yamaguchi F, Hatano N, Tokuda M: Prognostic significance of Jab1 expression in laryngeal squamous cell carcinomas. Clin Cancer Res 2005, 11: 259–266. 10.1158/1078-0432.CCR-04-1079 Wang F, Wang Y, Yu X, Yang D, Wang Z, Lu C, Yuan Z, Xiao M, Shen A: Significance of Jab1 expression in human esophageal squamous cell carcinoma. J Clin Gastroenterol 2009, 43: 520–526. 10.1097/MCG.0b013e3181919245 Ivan D, Diwan AH, Esteva FJ, Prieto VG: Expression of cell cycle inhibitor p27Kip1 and its inactivator Jab1 in melanocytic lesions. Mod Pathol 2004, 17: 811–818. 10.1038/modpathol.3800123 Rassidakis GZ, Claret FX, Lai R, Zhang Q, Sarris AH, McDonnell TJ, Medeiros LJ: Expression of p27(Kip1) and c-Jun activation binding protein 1 are inversely correlated in systemic anaplastic large cell lymphoma. Clin Cancer Res 2003, 9: 1121–1128. Wang Y, Fei M, Cheng C, Zhang D, Lu J, He S, Zhao Y, Shen A: Jun activation domain-binding protein 1 negatively regulate p27 kip1 in non-Hodgkin's lymphomas. Cancer Biol Ther 2008, 7: 460–467. 10.4161/cbt.7.3.5456 Ito Y, Yoshida H, Matsuzuka F, Matsuura N, Nakamura Y, Nakamine H, Kakudo K, Kuma K, Miyauchi A: Jun activation domain-binding protein 1 expression in malignant lymphoma of the thyroid: its linkage to degree of malignancy and p27 expression. Anticancer Res 2003, 23: 4121–4125. Ito Y, Yoshida H, Nakamura Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Kuma K, Kakudo K, Miyauchi A: Expression of Jun activation domain-binding protein 1 and p27 (Kip1) in thyroid medullary carcinoma. Pathology 2005, 37: 216–219. 10.1080/00313020500098959 Ahn J, Hong SA, Lee SE, Kim J, Oh YS, Park SJ, Chung YJ: Cytoplasmic localization of Jab1 and p27 Kip1 might be associated with invasiveness of papillary thyroid carcinoma. Endocr J 2009, 56: 707–713. 10.1507/endocrj.K08E-372 Osoegawa A, Yoshino I, Kometani T, Yamaguchi M, Kameyama T, Yohena T, Maehara Y: Overexpression of Jun activation domain-binding protein 1 in nonsmall cell lung cancer and its significance in p27 expression and clinical features. Cancer 2006, 107: 154–161. 10.1002/cncr.21961 Goto A, Niki T, Moriyama S, Funata N, Moriyama H, Nishimura Y, Tsuchida R, Kato JY, Fukayama M: Immunohistochemical study of Skp2 and Jab1, two key molecules in the degradation of P27, in lung adenocarcinoma. Pathol Int 2004, 54: 675–681. 10.1111/j.1440-1827.2004.01679.x