A portrayal of E3 ubiquitin ligases and deubiquitylases in cancer

International Journal of Cancer

Volumn 133, Issue 12, 2013, Pages 2759-2768

  Satija, Yatendra Kumar ^a   Bhardwaj, Abhishek ^a   Das, Sanjeev ^a  

^a NATIONAL INSTITUTE OF IMMUNOLOGY   (India)

Author keywords

cancer; p53; proteasome; ubiquitylation

Indexed keywords

BRCA1 PROTEIN; CULLIN; DNA; F BOX PROTEIN; LIGASE; ONCOPROTEIN; PROTEASOME; PROTEIN KINASE C; PROTEIN MDM2; PROTEIN P53; RING FINGER PROTEIN; RNA POLYMERASE II; S PHASE KINASE ASSOCIATED PROTEIN; SERINE; TATA BINDING PROTEIN; THREONINE; UBIQUITIN PROTEIN LIGASE; UBIQUITIN PROTEIN LIGASE COP1; UBIQUITIN PROTEIN LIGASE E3; UBIQUTIN SPECIFIC PROTEASE 10; UNCLASSIFIED DRUG;

CANCER INHIBITION; CELL CYCLE; CELL CYCLE REGULATION; CELLULAR STRESS RESPONSE; CHROMATIN ASSEMBLY AND DISASSEMBLY; DNA REPAIR; HUMAN; HYPOXIA; NEOPLASM; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN HOMEOSTASIS; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; UBIQUITINATION;

CANCER; P53; PROTEASOME; UBIQUITYLATION;

ANIMALS; BRCA1 PROTEIN; HUMANS; NEOPLASMS; PROTO-ONCOGENE PROTEINS C-MDM2; THIOLESTER HYDROLASES; TUMOR SUPPRESSOR PROTEIN P53; UBIQUITIN; UBIQUITIN THIOLESTERASE; UBIQUITIN-PROTEIN LIGASES; UBIQUITINATION;

EID: 84885642498     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.28129     Document Type: Review

References (126)

1. Hershko A,. Ubiquitin: roles in protein modification and breakdown. Cell 1983; 34: 11-2.
2. Okamoto Y, Ozaki T, Miyazaki K, et al. UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme. Cancer Res 2003; 63: 4167-73.
3. Nakayama KI, Nakayama K,. Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 2006; 6: 369-81.
4. Lipkowitz S, Weissman AM,. RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nat Rev Cancer 2011; 11: 629-43.
5. Levine AJ,. p53, the cellular gatekeeper for growth and division. Cell 1997; 88: 323-31.
6. Vogelstein B, Lane D, Levine AJ,. Surfing the p53 network. Nature 2000; 408: 307-10.
7. Oren M,. Decision making by p53: life, death and cancer. Cell Death Differ 2003; 10: 431-42.
8. Pickart CM,. Mechanisms underlying ubiquitination. Ann Rev Biochem 2001; 70: 503-33.
9. Ang XL, Wade Harper J,. SCF-mediated protein degradation and cell cycle control. Oncogene 2005; 24: 2860-70.
10. Huang L, Kinnucan E, Wang G, et al. Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade. Science 1999; 286: 1321-6.
11. Verdecia MA, Joazeiro CA, Wells NJ, et al. Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase. Mol Cell 2003; 11: 249-59.
12. Honda R, Tanaka H, Yasuda H,. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 1997; 420: 25-7.
13. Olson DC, Marechal V, Momand J, et al. Identification and characterization of multiple mdm-2 proteins and mdm-2-p53 protein complexes. Oncogene 1993; 8: 2353-60.
14. Vousden KH, Lu X,. Live or let die: the cell's response to p53. Nat Rev Cancer 2002; 2: 594-604.
15. Li M, Chen D, Shiloh A, et al. Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature 2002; 416: 648-53.
16. Shieh SY, Ikeda M, Taya Y, et al. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 1997; 91: 325-34.
17. Fang S, Jensen JP, Ludwig RL, et al. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem 2000; 275: 8945-51.
18. Rayburn E, Zhang R, He J, et al. MDM2 and human malignancies: expression, clinical pathology, prognostic markers, and implications for chemotherapy. Curr Cancer Drug Targets 2005; 5: 27-41.
19. Wei W, Kaelin WG, Jr., Good COP1 or bad COP1? In vivo veritas. J Clin Invest 2011; 121: 1263-5.
20. Dornan D, Wertz I, Shimizu H, et al. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature 2004; 429: 86-92.
21. Dornan D, Shimizu H, Mah A, et al. ATM engages autodegradation of the E3 ubiquitin ligase COP1 after DNA damage. Science 2006; 313: 1122-6.
22. Dornan D, Bheddah S, Newton K, et al. COP1, the negative regulator of p53, is overexpressed in breast and ovarian adenocarcinomas. Cancer Res 2004; 64: 7226-30.
23. Leng RP, Lin Y, Ma W, et al. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell 2003; 112: 779-91.
24. Duan W, Gao L, Druhan LJ, et al. Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer. J Natl Cancer Instit 2004; 96: 1718-21.
25. Logan IR, Gaughan L, McCracken SR, et al. Human PIRH2 enhances androgen receptor signaling through inhibition of histone deacetylase 1 and is overexpressed in prostate cancer. Mol Cell Biol 2006; 26: 6502-10.
26. Wang XM, Yang LY, Guo L, et al. p53-induced RING-H2 protein, a novel marker for poor survival in hepatocellular carcinoma after hepatic resection. Cancer 2009; 115: 4554-63.
27. Shimada M, Kitagawa K, Dobashi Y, et al. High expression of Pirh2, an E3 ligase for p27, is associated with low expression of p27 and poor prognosis in head and neck cancers. Cancer Sci 2009; 100: 866-72.
28. Sheng Y, Laister RC, Lemak A, et al. Molecular basis of Pirh2-mediated p53 ubiquitylation. Nat Struct Mol Biol 2008; 15: 1334-42.
29. Wang Z, Yang B, Dong L, et al. A novel oncoprotein Pirh2: rising from the shadow of MDM2. Cancer Sci 2011; 102: 909-17.
30. Jung YS, Hakem A, Hakem R, et al. Pirh2 E3 ubiquitin ligase monoubiquitinates DNA polymerase eta to suppress translesion DNA synthesis. Mol Cell Biol 2011; 31: 3997-4006.
31. Chen D, Kon N, Li M, et al. ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor. Cell 2005; 121: 1071-83.
32. Yoon SY, Lee Y, Kim JH, et al. Over-expression of human UREB1 in colorectal cancer: HECT domain of human UREB1 inhibits the activity of tumor suppressor p53 protein. Biochem Biophys Res Commun 2005; 326: 7-17.
33. Esser C, Scheffner M, Hohfeld J,. The chaperone-associated ubiquitin ligase CHIP is able to target p53 for proteasomal degradation. J Biol Chem 2005; 280: 27443-8.
34. Sisoula C, Trachana V, Patterson C, et al. CHIP-dependent p53 regulation occurs specifically during cellular senescence. Free Radic Biol Med 2011; 50: 157-65.
35. Sun L, Shi L, Wang F, et al. Substrate phosphorylation and feedback regulation in JFK-promoted p53 destabilization. J Biol Chem 2011; 286: 4226-35.
36. Sun L, Shi L, Li W, Yu W, Liang J, Zhang H, Yang X, Wang Y, Li R, Yao X, Yi X, Shang Y. JFK, a Kelch domain-containing F-box protein, links the SCF complex to p53 regulation. Proc Natl Acad Sci USA 2009; 106: 10195-200.
37. Yamasaki S, Yagishita N, Sasaki T, Nakazawa M, Kato Y, Yamadera T, Bae E, Toriyama S, Ikeda R, Zhang L, Fujitani K, Yoo E, et al. Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin'. EMBO J 2007; 26: 113-22.
38. Yamasaki S, Yagishita N, Nishioka K, Nakajima T. The roles of synoviolin in crosstalk between endoplasmic reticulum stress-induced apoptosis and p53 pathway. Cell Cycle 2007; 6: 1319-23.
39. Lee EW, Lee MS, Camus S, et al. Differential regulation of p53 and p21 by MKRN1 E3 ligase controls cell cycle arrest and apoptosis. EMBO J 2009; 28: 2100-13.
40. Feldman RM, Correll CC, Kaplan KB, et al. A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell 1997; 91: 221-30.
41. Cardozo T, Pagano M,. The SCF ubiquitin ligase: insights into a molecular machine. Nat Rev Mol Cell Biol 2004; 5: 739-51.
42. Bai C, Sen P, Hofmann K, et al. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell 1996; 86: 263-74.
43. Nalepa G, Rolfe M, Harper JW,. Drug discovery in the ubiquitin-proteasome system. Nature reviews. Drug Discov 2006; 5: 596-613.
44. Kraus B, Pohlschmidt M, Leung AL, et al. A novel cyclin gene (CCNF) in the region of the polycystic kidney disease gene (PKD1). Genomics 1994; 24: 27-33.
45. Cenciarelli C, Chiaur DS, Guardavaccaro D, et al. Identification of a family of human F-box proteins. Curr Biol 1999; 9: 1177-9.
46. Petroski MD, Deshaies RJ,. Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol 2005; 6: 9-20.
47. Sarikas A, Hartmann T, Pan ZQ,. The cullin protein family. Genome Biol 2011; 12: 220.
48. Kamura T, Maenaka K, Kotoshiba S, et al. VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes Dev 2004; 18: 3055-65.
49. Deshaies RJ, Emberley ED, Saha A,. Control of cullin-ring ubiquitin ligase activity by nedd8. Subcell Biochem 2010; 54: 41-56.
50. Xirodimas DP, Saville MK, Bourdon JC, et al. Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell 2004; 118: 83-97.
51. Dye BT, Schulman BA,. Structural mechanisms underlying posttranslational modification by ubiquitin-like proteins. Annu Rev Biophys Biomol Struct 2007; 36: 131-50.
52. Carrano AC, Eytan E, Hershko A, et al. SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nat Cell Biol 1999; 1: 193-9.
53. Bornstein G, Bloom J, Sitry-Shevah D, et al. Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase. J Biol Chem 2003; 278: 25752-7.
54. Kitagawa M, Lee SH, McCormick F,. Skp2 suppresses p53-dependent apoptosis by inhibiting p300. Mol Cell 2008; 29: 217-31.
55. Tedesco D, Lukas J, Reed SI,. The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCF(Skp2). Genes Dev 2002; 16: 2946-57.
56. Kamura T, Hara T, Kotoshiba S, et al. Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylation. Proc Natl Acad Sci USA 2003; 100: 10231-6.
57. Hiramatsu Y, Kitagawa K, Suzuki T, et al. Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination. Cancer Res 2006; 66: 8477-83.
58. Song MS, Song SJ, Kim SJ, et al. Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via ubiquitin-mediated degradation at the G1-S transition. Oncogene 2008; 27: 3176-85.
59. Huang H, Regan KM, Wang F, et al. Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. Proc Natl Acad Sci USA 2005; 102: 1649-54.
60. Gstaiger M, Jordan R, Lim M, et al. Skp2 is oncogenic and overexpressed in human cancers. Proc Natl Acad Sci USA 2001; 98: 5043-8.
61. Signoretti S, Di Marcotullio L, Richardson A, et al. Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer. J Clin Invest 2002; 110: 633-41.
62. Calvisi DF, Ladu S, Pinna F, et al. SKP2 and CKS1 promote degradation of cell cycle regulators and are associated with hepatocellular carcinoma prognosis. Gastroenterology 2009; 137: 1816-26 e1-e10.
63. Shin E, Kim SH, Jeong HY, et al. Nuclear expression of S-phase kinase-associated protein 2 predicts poor prognosis of hepatocellular carcinoma. APMIS 2012; 120: 349-57.
64. Ougolkov A, Zhang B, Yamashita K, et al. Associations among beta-TrCP, an E3 ubiquitin ligase receptor, beta-catenin, and NF-kappaB in colorectal cancer. J Natl Cancer Instit 2004; 96: 1161-70.
65. Muerkoster S, Arlt A, Sipos B, et al. Increased expression of the E3-ubiquitin ligase receptor subunit betaTRCP1 relates to constitutive nuclear factor-kappaB activation and chemoresistance in pancreatic carcinoma cells. Cancer Res 2005; 65: 1316-24.
66. Koch A, Waha A, Hartmann W, et al. Elevated expression of Wnt antagonists is a common event in hepatoblastomas. Clin Cancer Res 2005; 11: 4295-304.
67. Spiegelman VS, Tang W, Chan AM, et al. Induction of homologue of Slimb ubiquitin ligase receptor by mitogen signaling. J Biol Chem 2002; 277: 36624-30.
68. Tan P, Fuchs SY, Chen A, et al. Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of I kappa B alpha. Mol Cell 1999; 3: 527-33.
69. Watanabe N, Arai H, Nishihara Y, et al. M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP. Proc Natl Acad Sci USA 2004; 101: 4419-24.
70. Busino L, Donzelli M, Chiesa M, et al. Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature 2003; 426: 87-91.
71. Liu C, Kato Y, Zhang Z, et al. beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation. Proc Natl Acad Sci USA 1999; 96: 6273-8.
72. Wood LD, Parsons DW, Jones S, et al. The genomic landscapes of human breast and colorectal cancers. Science 2007; 318: 1108-13.
73. Maser RS, Choudhury B, Campbell PJ, et al. Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature 2007; 447: 966-71.
74. Koepp DM, Schaefer LK, Ye X, et al. Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science 2001; 294: 173-7.
75. Welcker M, Orian A, Jin J, et al. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc Natl Acad Sci USA 2004; 101: 9085-90.
76. Wei W, Jin J, Schlisio S, et al. The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase. Cancer Cell 2005; 8: 25-33.
77. Venkitaraman AR,. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 2002; 108: 171-82.
78. Fang S, Lorick KL, Jensen JP, et al. RING finger ubiquitin protein ligases: implications for tumorigenesis, metastasis and for molecular targets in cancer. Semin Cancer Biol 2003; 13: 5-14.
79. Fackenthal JD, Olopade OI,. Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations. Nat Rev Cancer 2007; 7: 937-48.
80. Brzovic PS, Rajagopal P, Hoyt DW, et al. Structure of a BRCA1-BARD1 heterodimeric RING-RING complex. Nat Struct Biol 2001; 8: 833-7.
81. Huen MS, Sy SM, Chen J,. BRCA1 and its toolbox for the maintenance of genome integrity. Nat Rev Mol Cell Biol 2010; 11: 138-48.
82. Galanty Y, Belotserkovskaya R, Coates J, et al. Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks. Nature 2009; 462: 935-9.
83. Yu X, Fu S, Lai M, et al. BRCA1 ubiquitinates its phosphorylation- dependent binding partner CtIP. Genes Dev 2006; 20: 1721-6.
84. Eakin CM, Maccoss MJ, Finney GL, et al. Estrogen receptor alpha is a putative substrate for the BRCA1 ubiquitin ligase. Proc Natl Acad Sci USA 2007; 104: 5794-9.
85. Poole AJ, Li Y, Kim Y, et al. Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist. Science 2006; 314: 1467-70.
86. Fan S, Ma YX, Wang C, et al. Role of direct interaction in BRCA1 inhibition of estrogen receptor activity. Oncogene 2001; 20: 77-87.
87. Katiyar P, Ma Y, Riegel A, et al. Mechanism of BRCA1-mediated inhibition of progesterone receptor transcriptional activity. Mol Endocrinol 2009; 23: 1135-46.
88. Ma Y, Fan S, Hu C, et al. BRCA1 regulates acetylation and ubiquitination of estrogen receptor-alpha. Mol Endocrinol 2010; 24: 76-90.
89. Zhu Q, Pao GM, Huynh AM, et al. BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nature 2011; 477: 179-84.
90. Latif F, Tory K, Gnarra J, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 1993; 260: 1317-20.
91. Herman JG, Graff JR, Myohanen S, et al. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA 1996; 93: 9821-6.
92. Gnarra JR, Tory K, Weng Y, et al. Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet 1994; 7: 85-90.
93. Kibel A, Iliopoulos O, DeCaprio JA, et al. Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C. Science 1995; 269: 1444-6.
94. Pause A, Lee S, Worrell RA, et al. The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins. Proc Natl Acad Sci USA 1997; 94: 2156-61.
95. Kamura T, Koepp DM, Conrad MN, et al. Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science 1999; 284: 657-61.
96. Ohh M, Park CW, Ivan M, et al. Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol 2000; 2: 423-7.
97. Zhang Q, Yang H,. The roles of VHL-dependent ubiquitination in signaling and cancer. Front Oncol 2012; 2: 35.
98. Cao R, Tsukada Y, Zhang Y,. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell 2005; 20: 845-54.
99. Wang H, Wang L, Erdjument-Bromage H, et al. Role of histone H2A ubiquitination in Polycomb silencing. Nature 2004; 431: 873-8.
100. Sen N, Satija YK, Das S,. PGC-1alpha, a key modulator of p53, promotes cell survival upon metabolic stress. Mol Cell 2011; 44: 621-34.
101. Li M, Brooks CL, Kon N, et al. A dynamic role of HAUSP in the p53-Mdm2 pathway. Mol Cell 2004; 13: 879-86.
102. Song MS, Salmena L, Carracedo A, et al. The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature 2008; 455: 813-7.
103. Yuan J, Luo K, Zhang L, et al. USP10 regulates p53 localization and stability by deubiquitinating p53. Cell 2010; 140: 384-96.
104. Jochemsen AG, Shiloh Y,. USP10: friend and foe. Cell 2010; 140: 308-10.
105. Boyd SD, Tsai KY, Jacks T,. An intact HDM2 RING-finger domain is required for nuclear exclusion of p53. Nat Cell Biol 2000; 2: 563-8.
106. Freedman DA, Levine AJ,. Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6. Mol Cell Biol 1998; 18: 7288-93.
107. Geyer RK, Yu ZK, Maki CG,. The MDM2 RING-finger domain is required to promote p53 nuclear export. Nat Cell Biol 2000; 2: 569-73.
108. Li M, Brooks CL, Wu-Baer F, et al. Mono-versus polyubiquitination: differential control of p53 fate by Mdm2. Science 2003; 302: 1972-5.
109. Glinsky GV,. Genomic models of metastatic cancer: functional analysis of death-from-cancer signature genes reveals aneuploid, anoikis-resistant, metastasis-enabling phenotype with altered cell cycle control and activated Polycomb Group (PcG) protein chromatin silencing pathway. Cell Cycle 2006; 5: 1208-16.
110. Sowa ME, Bennett EJ, Gygi SP, et al. Defining the human deubiquitinating enzyme interaction landscape. Cell 2009; 138: 389-403.
111. Zhang XY, Pfeiffer HK, Thorne AW, et al. USP22, an hSAGA subunit and potential cancer stem cell marker, reverses the polycomb-catalyzed ubiquitylation of histone H2A. Cell Cycle 2008; 7: 1522-4.
112. Joo HY, Zhai L, Yang C, et al. Regulation of cell cycle progression and gene expression by H2A deubiquitination. Nature 2007; 449: 1068-72.
113. Atanassov BS, Dent SY,. USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1. EMBO Rep 2011; 12: 924-30.
114. Zalmas LP, Zhao X, Graham AL, et al. DNA-damage response control of E2F7 and E2F8. EMBO Rep 2008; 9: 252-9.
115. Lin Z, Yang H, Kong Q, et al. USP22 antagonizes p53 transcriptional activation by deubiquitinating Sirt1 to suppress cell apoptosis and is required for mouse embryonic development. Mol Cell 2012; 46: 484-94.
116. Lee HJ, Kim MS, Shin JM, et al. The expression patterns of deubiquitinating enzymes, USP22 and Usp22. Gene Expr Patterns 2006; 6: 277-84.
117. Glinsky GV, Berezovska O, Glinskii AB,. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest 2005; 115: 1503-21.
118. Zhang XY, Varthi M, Sykes SM, et al. The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Mol Cell 2008; 29: 102-11.
119. Liu YL, Jiang SX, Yang YM, et al. USP22 acts as an oncogene by the activation of BMI-1-mediated INK4a/ARF pathway and Akt pathway. Cell Biochem Biophys 2012; 62: 229-35.
120. Stevenson LF, Sparks A, Allende-Vega N, et al. The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2. EMBO J 2007; 26: 976-86.
121. Allende-Vega N, Sparks A, Lane DP, et al. MdmX is a substrate for the deubiquitinating enzyme USP2a. Oncogene 2010; 29: 432-41.
122. Graner E, Tang D, Rossi S, et al. The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer. Cancer Cell 2004; 5: 253-61.
123. Shan J, Zhao W, Gu W,. Suppression of cancer cell growth by promoting cyclin D1 degradation. Mol Cell 2009; 36: 469-76.
124. Kim J, Kim WJ, Liu Z, et al. The ubiquitin-specific protease USP2a enhances tumor progression by targeting cyclin A1 in bladder cancer. Cell Cycle 2012; 11: 1123-30.
125. Priolo C, Tang D, Brahamandan M, et al. The isopeptidase USP2a protects human prostate cancer from apoptosis. Cancer Res 2006; 66: 8625-32.
126. Selvendiran K, Ahmed S, Dayton A, et al. HO-3867, a synthetic compound, inhibits the migration and invasion of ovarian carcinoma cells through downregulation of fatty acid synthase and focal adhesion kinase. Mol Cancer Res 2010; 8: 1188-97.