Small RING finger proteins RBX1 and RBX2 of SCF E3 ubiquitin ligases: The role in cancer and as cancer targets

Genes and Cancer

Volumn 1, Issue 7, 2010, Pages 700-707

  Wei, Dongping ^a   Sun, Yi ^a  

^a UNIVERSITY OF MICHIGAN COMPREHENSIVE CANCER CENTER   (United States)

Author keywords

Anticancer targets; Neddylation; Protein degradation; RING box proteins; SCF E3 ubiquitin ligases; Ubiquitin proteasome system

Indexed keywords

ANTINEOPLASTIC AGENT; CULLIN; MLN 4924; NEDD8 PROTEIN; PROTEASOME; PROTEIN C JUN; RING BOX PROTEIN 1; RING BOX PROTEIN 2; RING FINGER PROTEIN; S PHASE KINASE ASSOCIATED PROTEIN 2; SENSITIVE TO APOPTOSIS PROTEIN; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR AP 1; UBIQUITIN PROTEIN LIGASE; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CANCER SURVIVAL; CARCINOGENESIS; CATALYSIS; CELL AGING; CELL CYCLE S PHASE; CELL GROWTH; CELL SURVIVAL; CRYSTAL STRUCTURE; DRUG TOLERABILITY; EMBRYO DEVELOPMENT; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME REGULATION; GENE SILENCING; GENE STRUCTURE; HEMATOLOGIC MALIGNANCY; HUMAN; MALIGNANT NEOPLASTIC DISEASE; MOLECULAR CLONING; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROCESSING; PROTEIN STRUCTURE; PROTEIN TARGETING; SENESCENCE; SKIN CARCINOGENESIS; SOLID TUMOR; TISSUE DISTRIBUTION; TRANSCRIPTION REGULATION; UBIQUITINATION;

EID: 79952853588     PISSN: 19476019     EISSN: 19476027     Source Type: Journal    
DOI: 10.1177/1947601910382776     Document Type: Article

References (99)

1. Kerscher O, Felberbaum R, Hochstrasser M. Modification of proteins by ubiquitin and ubiquitin-like proteins. Annu Rev Cell Dev Biol. 2006;22:159-80.
2. Nalepa G, Rolfe M, Harper JW. Drug discovery in the ubiquitin-proteasome system. Nat Rev Drug Discov. 2006;5:596-613.
3. Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem. 1998;67:425-79.
4. Chen ZJ, Sun LJ. Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell. 2009;33:275-86.
5. Skaug B, Jiang X, Chen ZJ. The role of ubiquitin in NF-kappaB regulatory pathways. Annu Rev Biochem. 2009;78:769-96.
6. Bennett EJ, Harper JW. DNA damage: ubiquitin marks the spot. Nat Struct Mol Biol. 2008;15: 20-2.
7. Ulrich HD, Walden H. Ubiquitin signalling in DNA replication and repair. Nat Rev Mol Cell Biol. 2010;11:479-89.
8. Acconcia F, Sigismund S, Polo S. Ubiquitin in trafficking: the network at work. Exp Cell Res. 2009;315:1610-8.
9. Hicke L, Schubert HL, Hill CP. Ubiquitinbinding domains. Nat Rev Mol Cell Biol. 2005;6: 610-21.
10. Pickart CM. Ubiquitin enters the new millennium. Mol Cell. 2001;8:499-504.
11. Nagy V, Dikic I. Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity. Biol Chem. 2010;391:163-9.
12. Deshaies RJ, Joazeiro CA. RING domain E3 ubiquitin ligases. Annu Rev Biochem. 2009;78:399-434.
13. Willems AR, Schwab M, Tyers M. A hitchhiker's guide to the cullin ubiquitin ligases: SCF and its kin. Biochim Biophys Acta. 2004;1695:133-70.
14. Nakayama KI, Nakayama K. Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer. 2006;6:369-81.
15. Petroski MD, Deshaies RJ. Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol. 2005;6:9-20.
16. 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.
17. Ohta T, Michel JJ, Schottelius AJ, Xiong Y. ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Mol Cell. 1999;3:535-41.
18. Seol JH, Feldman RMR, Zachariae WZ, et al. Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34. Genes Dev. 1999;13:1614-26.
19. Tan P, Fuchs SY, Chen A, et al. Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of IkBa. Mol Cell. 1999;3:527-33.
20. Tan M, Davis SW, Saunders TL, Zhu Y, Sun Y. RBX1/ROC1 disruption results in early embryonic lethality due to proliferation failure, partially rescued by simultaneous loss of p27. Proc Natl Acad Sci U S A. 2009;106:6203-8.
21. Sun Y, Tan M, Duan H, Swaroop M. SAG/ ROC/Rbx/Hrt, a zinc RING finger gene family: molecular cloning, biochemical properties, and biological functions. Antioxid Redox Signal. 2001;3:635-50.
22. Chen A, Wu K, Fuchs SY, Tan P, Gomez C, Pan ZQ. The conserved RING-H2 finger of ROC1 is required for ubiquitin ligation. J Biol Chem. 2000;275:15432-9.
23. Ohta T, Michel JJ, Xiong Y. Association with cullin partners protects ROC proteins from proteasome-dependent degradation. Oncogene. 1999;18:6758-66.
24. Duan H, Wang Y, Aviram M, et al. SAG, a novel zinc RING finger protein that protects cells from apoptosis induced by redox agents. Mol Cell Biol. 1999;19:3145-55.
25. Swaroop M, Bian J, Aviram M, et al. Expression, purification, and biochemical characterization of SAG, a RING finger redox sensitive protein. Free Radicals Biol Med. 1999;27:193-202.
26. Swaroop M, Gosink M, Sun Y. SAG/ROC2/ Rbx2/Hrt2, a component of SCF E3 ubiquitin ligase: genomic structure, a splicing variant, and two family pseudogenes. DNA Cell Biol. 2001;20:425-34.
27. Swaroop M, Wang Y, Miller P, et al. Yeast homolog of human SAG/ROC2/Rbx2/Hrt2 is essential for cell growth, but not for germination: chip profiling implicates its role in cell cycle regulation. Oncogene. 2000;19:2855-66.
28. Tan M, Gu Q, He H, Pamarthy D, Semenza GL, Sun Y. SAG/ROC2/RBX2 is a HIF-1 target gene that promotes HIF-1alpha ubiquitination and degradation. Oncogene. 2008;27:1404-11.
29. Yang ES, Park JW. Regulation of nitric oxideinduced apoptosis by sensitive to apoptosis gene protein. Free Radic Res. 2006;40:279-84.
30. Chanalaris A, Sun Y, Latchman DS, Stephanou A. SAG attenuates apoptotic cell death caused by simulated ischaemia/reoxygenation in rat cardiomyocytes. J Mol Cell Cardiol. 2003;35:257-64.
31. Yang GY, Pang L, Ge HL, et al. Attenuation of ischemia-induced mouse brain injury by SAG, a redox-inducible antioxidant protein. J Cereb Blood Flow Metab. 2001;21:722-33.
32. Kim SY, Kim MY, Mo JS, Park JW, Park HS. SAG protects human neuroblastoma SH-SY5Y cells against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity via the downregulation of ROS generation and JNK signaling. Neurosci Lett. 2007;413:132-6.
33. Lee SJ, Yang ES, Kim SY, Shin SW, Park JW. Regulation of heat shock-induced apoptosis by sensitive to apoptosis gene protein. Free Radic Biol Med. 2008;45:167-76.
34. Gu Q, Tan M, Sun Y. SAG/ROC2/Rbx2 is a novel activator protein-1 target that promotes c-Jun degradation and inhibits 12-O-tetradecanoylphorbol-13-acetate-induced neoplastic transformation. Cancer Res. 2007;67:3616-25.
35. He H, Gu Q, Zheng M, Normolle D, Sun Y. SAG/ ROC2/RBX2 E3 ligase promotes UVB-induced skin hyperplasia, but not skin tumors, by simultaneously targeting c-Jun/AP-1 and p27. Carcinogenesis. 2008;29:858-65.
36. Wingender E, Dietze P, Karas H, Knuppel R. TRANSFAC: a database on transcription factors and their DNA binding sites. Nucleic Acids Res. 1996;24:238-41.
37. Perin JP, Seddiqi N, Charbonnier F, et al. Genomic organization and expression of the ubiquitinproteasome complex-associated protein Rbx1/ ROC1/Hrt1. Cell Mol Biol. 1999;45:1131-7.
38. Jia L, Soengas MS, Sun Y. ROC1/RBX1 E3 ubiquitin ligase silencing suppresses tumor cell growth via sequential induction of G2-M arrest, apoptosis, and senescence. Cancer Res. 2009;69:4974-82.
39. Zheng N, Schulman BA, Song L, et al. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature. 2002;416:703-9.
40. Jin J, Cardozo T, Lovering RC, Elledge SJ, Pagano M, Harper JW. Systematic analysis and nomenclature of mammalian F-box proteins. Genes Dev. 2004;18:2573-80.
41. Wu K, Fuchs SY, Chen A, et al. The SCF(HOS/ beta-TRCP)-ROC1 E3 ubiquitin ligase utilizes two distinct domains within CUL1 for substrate targeting and ubiquitin ligation. Mol Cell Biol. 2000;20:1382-93.
42. 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.
43. Kamura T, Burian D, Yan Q, et al. Muf1, a novel Elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase. J Biol Chem. 2001;276:29748-53.
44. Cardozo T, Pagano M. The SCF ubiquitin ligase: insights into a molecular machine. Nat Rev Mol Cell Biol. 2004;5:739-51.
45. Jia L, Sun Y. RBX1/ROC1-SCF E3 ubiquitin ligase is required for mouse embryogenesis and cancer cell survival. Cell Div. 2009;4:16.
46. Pan ZQ, Kentsis A, Dias DC, Yamoah K, Wu K. Nedd8 on cullin: building an expressway to protein destruction. Oncogene. 2004;23:1985-97.
47. Rabut G, Peter M. Function and regulation of protein neddylation. 'Protein modifications: beyond the usual suspects' review series. EMBO Rep. 2008;9:969-76.
48. Xirodimas DP. Novel substrates and functions for the ubiquitin-like molecule NEDD8. Biochem Soc Trans. 2008;36:802-6.
49. Gong L, Yeh ET. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J Biol Chem. 1999;274:12036-42.
50. Liakopoulos D, Doenges G, Matuschewski K, Jentsch S. A novel protein modification pathway related to the ubiquitin system. EMBO J. 1998;17:2208-14.
51. Osaka F, Kawasaki H, Aida N, et al. A new NEDD8-ligating system for cullin-4A. Genes Dev. 1998;12:2263-8.
52. Huang DT, Ayrault O, Hunt HW, et al. E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol Cell. 2009;33: 483-95.
53. Kamura T, Conrad MN, Yan Q, Conaway RC, Conaway JW. The Rbx1 subunit of SCF and VHL E3 ubiquitin ligase activates Rub1 modification of cullins Cdc53 and Cul2. Genes Dev. 1999;13:2928-33.
54. Morimoto M, Nishida T, Nagayama Y, Yasuda H. Nedd8-modification of Cul1 is promoted by Roc1 as a Nedd8-E3 ligase and regulates its stability. Biochem Biophys Res Commun. 2003;301:392-8.
55. Yang X, Zhou J, Sun L, et al. Structural basis for the function of DCN-1 in protein neddylation. J Biol Chem. 2007;282:24490-4.
56. Kim AY, Bommelje CC, Lee BE, et al. SCCRO (DCUN1D1) is an essential component of the E3 complex for neddylation. J Biol Chem. 2008;283:33211-20.
57. Kurz T, Chou YC, Willems AR, et al. Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation. Mol Cell. 2008;29:23-35.
58. Duda DM, Borg LA, Scott DC, Hunt HW, Hammel M, Schulman BA. Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell. 2008;134:995-1006.
59. Goldenberg SJ, Cascio TC, Shumway SD, et al. Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases. Cell. 2004;119:517-28.
60. Yamoah K, Oashi T, Sarikas A, Gazdoiu S, Osman R, Pan ZQ. Autoinhibitory regulation of SCF-mediated ubiquitination by human cullin 1's C-terminal tail. Proc Natl Acad Sci U S A. 2008;105:12230-5.
61. Zheng J, Yang X, Harrell JM, et al. CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex. Mol Cell. 2002;10:1519-26.
62. Liu J, Furukawa M, Matsumoto T, Xiong Y. NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases. Mol Cell. 2002;10:1511-8.
63. Merlet J, Burger J, Gomes JE, Pintard L. Regulation of cullin-RING E3 ubiquitin-ligases by neddylation and dimerization. Cell Mol Life Sci. 2009;66:1924-38.
64. Soucy TA, Smith PG, Milhollen MA, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009;458:732-6.
65. Skaar JR, D'Angiolella V, Pagan JK, Pagano M. SnapShot: F box proteins II. Cell. 2009;137: 1358, e1351.
66. Welcker M, Clurman BE. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer. 2008;8:83-93.
67. Frescas D, Pagano M. Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer. Nat Rev Cancer. 2008;8:438-49.
68. Yen HC, Elledge SJ. Identification of SCF ubiquitin ligase substrates by global protein stability profiling. Science. 2008;322:923-9.
69. Yen HC, Xu Q, Chou DM, Zhao Z, Elledge SJ. Global protein stability profiling in mammalian cells. Science. 2008;322:918-23.
70. Sasagawa Y, Urano T, Kohara Y, Takahashi H, Higashitani A. Caenorhabditis elegans RBX1 is essential for meiosis, mitotic chromosomal condensation and segregation, and cytokinesis. Genes Cells. 2003;8:857-72.
71. Moore R, Boyd L. Analysis of RING finger genes required for embryogenesis in C. elegans. Genesis. 2004;38:1-12.
72. Donaldson TD, Noureddine MA, Reynolds PJ, Bradford W, Duronio RJ. Targeted disruption of Drosophila Roc1b reveals functional differences in the Roc subunit of Cullin-dependent E3 ubiquitin ligases. Mol Biol Cell. 2004;15: 4892-903.
73. Reynolds PJ, Simms JR, Duronio RJ. Identifying determinants of cullin binding specificity among the three functionally different Drosophila melanogaster Roc proteins via domain swapping. PLoS One. 2008;3:e2918.
74. Sasaki H, Yukiue H, Kobayashi Y, et al. Expression of the sensitive to apoptosis gene, SAG, as a prognostic marker in nonsmall cell lung cancer. Int J Cancer. 2001;95:375-7.
75. Huang Y, Duan H, Sun Y. Elevated expression of SAG/ROC2/Rbx2/Hrt2 in human colon carcinomas: SAG does not induce neoplastic transformation, but its antisense transfection inhibits tumor cell growth. Mol Carcinog. 2001;30:62-70.
76. Jia L, Yang J, Hao X, et al. Validation of SAG/ RBX2/ROC2 E3 ubiquitin ligase as an anticancer and radiosensitizing target. Clin Cancer Res. 2010;16:814-24.
77. Gu Q, Bowden TG, Normolle D, Sun Y. SAG/ ROC2 E3 ligase regulates skin carcinogenesis by stage dependent targeting of c-Jun/AP1 and IkB/ NF-kB. J Cell Biol. 2007;178:1009-23.
78. Sun Y. E3 ubiquitin ligases as cancer targets and biomarkers. Neoplasia. 2006;8:645-54.
79. Sun Y. Alteration of SAG mRNA in human cancer cell lines: requirement for the RING finger domain for apoptosis protection. Carcinogenesis. 1999;20:1899-903.
80. Kim DW, Lee SH, Jeong MS, et al. Transduced Tat-SAG fusion protein protects against oxidative stress and brain ischemic insult. Free Radic Biol Med. 2010;48:969-77.
81. Duan H, Tsvetkov LM, Liu Y, et al. Promotion of S-phase entry and cell growth under serum starvation by SAG/ROC2/Rbx2/Hrt2, an E3 ubiquitin ligase component: association with inhibition of p27 accumulation. Mol Carcinog. 2001;30:37-46.
82. Tan M, Gallegos JR, Gu Q, et al. SAG/ROCSCFbeta- TrCP E3 ubiquitin ligase promotes pro-caspase-3 degradation as a mechanism of apoptosis protection. Neoplasia. 2006;8:1042-54.
83. Tan M, Zhu Y, Kovacev J, et al. Disruption of SAG/RBX2/ROC2 induces radiosensitization by increasing ROS levels and blocking NF-kB activation in mouse embryonic stem cells. Free Radic Biol Med. 2010;49:976-83.
84. Campisi J, d'Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007;8:729-40.
85. Deng Y, Chan SS, Chang S. Telomere dysfunction and tumour suppression: the senescence connection. Nat Rev Cancer. 2008;8:450-8.
86. Itahana K, Campisi J, Dimri GP. Mechanisms of cellular senescence in human and mouse cells. Biogerontology. 2004;5:1-10.
87. Li X, Zhao Q, Liao R, Sun P, Wu X. The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation. J Biol Chem. 2003;278:30854-8.
88. Mendez J, Zou-Yang XH, Kim SY, Hidaka M, Tansey WP, Stillman B. Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication. Mol Cell. 2002;9:481-91.
89. Hu J, Xiong Y. An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by the Cul4-Ddb1 ubiquitin ligase in response to DNA damage. J Biol Chem. 2006;281:3753-6.
90. Nishitani H, Sugimoto N, Roukos V, et al. Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. EMBO J. 2006;25:1126-36.
91. Bell SP. The origin recognition complex: from simple origins to complex functions. Genes Dev. 2002;16:659-72.
92. Speck C, Chen Z, Li H, Stillman B. ATPasedependent cooperative binding of ORC and Cdc6 to origin DNA. Nat Struct Mol Biol. 2005;12:965-71.
93. Liontos M, Koutsami M, Sideridou M, et al. Deregulated overexpression of hCdt1 and hCdc6 promotes malignant behavior. Cancer Res. 2007;67:10899-909.
94. Sun Y. Targeting E3 ubiquitin ligases for cancer therapy. Cancer Biol Therapy. 2003;2:623-9.
95. Sun Y. Overview of approaches for screening for ubiquitin ligase inhibitors. Methods Enzymol. 2005;399:654-63.
96. Brownell JE, Sintchak MD, Gavin JM, et al. Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ. Mol Cell. 2010;37:102-11.
97. Swords RT, Kelly KR, Smith PG, et al. Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia. Blood. 2010;115:3796-800.
98. Lin HK, Chen Z, Wang G, et al. Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature. 2010;464:374-9.
99. Soucy TA, Smith PG, Rolfe M. Targeting NEDD8- activated cullin-RING ligases for the treatment of cancer. Clin Cancer Res. 2009;15: 3912-6.