Genetic and expression aberrations of E3 ubiquitin ligases in human breast cancer

Molecular Cancer Research

Volumn 4, Issue 10, 2006, Pages 695-707

  Chen, Ceshi ^a   Seth, Arun K ^b   Aplin, Andrew E ^a  

^a ALBANY MEDICAL COLLEGE   (United States)

^b SUNNYBROOK RESEARCH INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

APC PROTEIN; ARF BINDING PROTEIN 1; BCA ASSOCIATED RING DOMAIN PROTEIN 2; BETA TRANSDUCIN REPEAT CONTAINING PROTEIN; BORTEZOMIB; BRCA1 ASSOCIATED RING DOMAIN PROTEIN 1; BRCA1 PROTEIN; BROAD COMPLEX BOX PROTEIN; CELL CYCLE PROTEIN; CULLIN; CULLIN 4A; CULLIN 5; F BOX PROTEIN; GROWTH FACTOR; HOMOLOGOUS TO E6 ASSOCIATED PROTEIN CARBOXY TERMINUS ENZYME; PARKIN; PLANT HOMEO DOMAIN ENZYME; PROTEIN MDM2; PROTEIN P53; PROTEIN SUBUNIT; REALLY INTERESTING NEW GENE FINGER ENZYME; RING FINGER PROTEIN 11; S PHASE KINASE ASSOCIATED PROTEIN 2; SUPPRESSOR OF CELL SIGNALING BOX PROTEIN; U BOX ENZYME; UBIQUITIN PROTEIN LIGASE E3; UBIQUITIN PROTEIN LIGASE NEDD4; UNCLASSIFIED DRUG; X LINKED INHIBITOR OF APOPTOSIS;

APOPTOSIS; BCA2 GENE; BREAST CANCER; CARCINOGENESIS; CELL COMMUNICATION; CELL CYCLE REGULATION; CHFR GENE; CHIP GENE; COMPLEX FORMATION; DNA REPAIR; EFP GENE; ENZYME SPECIFICITY; GENE AMPLIFICATION; GENE DELETION; GENE MUTATION; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; HUMAN; METHYLATION; NONHUMAN; ONCOGENE; PARKIN GENE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN DOMAIN; REVIEW; SIAH1 GENE; TUMOR SUPPRESSOR GENE; UNSPECIFIED SIDE EFFECT; WWP1 GENE;

BREAST NEOPLASMS; CHROMOSOME ABERRATIONS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENES, TUMOR SUPPRESSOR; HUMANS; MODELS, BIOLOGICAL; ONCOGENES; PROTEASOME ENDOPEPTIDASE COMPLEX; SIGNAL TRANSDUCTION; UBIQUITIN-PROTEIN LIGASE COMPLEXES; UBIQUITIN-PROTEIN LIGASES;

EID: 33750590972     PISSN: 15417786     EISSN: None     Source Type: Journal    
DOI: 10.1158/1541-7786.MCR-06-0182     Document Type: Review

References (204)

1. American Cancer Society. Cancer facts and figures 2006. Oakland (CA): American Cancer Society; 2006.
2. Sinclair CS, Rowley M, Naderi A, Couch FJ. The 17q23 amplicon and breast cancer. Breast Cancer Res Treat 2003;78:313-22.
3. Guan XY, Xu J, Anzick SL, Zhang H, Trent JM, Meltzer PS. Hybrid selection of transcribed sequences from microdissected DNA: isolation of genes within amplified region at 20q11-13.2 in breast cancer. Cancer Res 1996;56:3446-50.
4. Yaremko ML, Kutza C, Lyzak J, Mick R, Recant WM, Westbrook CA. Loss of heterozygosity from the short arm of chromosome 8 is associated with invasive behavior in breast cancer. Genes Chromosomes Cancer 1996;16:189-95.
5. Laake K, Launonen V, Niederacher D, et al. Loss of heterozygosity at 11q23.1 and survival in breast cancer: results of a large European study. Breast Cancer Somatic Genetics Consortium. Genes Chromosomes Cancer 1999;25:212-21.
6. Iida A, Isobe R, Yoshimoto M, Kasumi F, Nakamura Y, Emi M. Localization of a breast cancer tumour-suppressor gene to a 3-cM interval within chromosomal region 16q22. Br J Cancer 1997;75:264-7.
7. Mielnicki LM, Asch HL, Asch BB. Genes, chromatin, and breast cancer: an epigenetic tale. J Mammary Gland Biol Neoplasia 2001;6:169-82.
8. Muratani M, Tansey WP. How the ubiquitin-proteasome system controls transcription. Nat Rev Mol Cell Biol 2003;4:192-201.
9. Zhang HG, Wang J, Yang X, Hsu HC, Mountz JD. Regulation of apoptosis proteins in cancer cells by ubiquitin. Oncogene 2004;23:2009-15.
10. Mani A, Gelmann EP. The ubiquitin-proteasome pathway and its role in cancer. J Clin Oncol 2005;23:4776-89.
11. Devoy A, Soane T, Welchman R, Mayer RJ. The ubiquitin-proteasome system and cancer. Essays Biochem 2005;41:187-203.
12. Ohta T, Fukuda M. Ubiquitin and breast cancer. Oncogene 2004;23:2079-88.
13. Cardoso F, Ross JS, Picart MJ, Sotiriou C, Durbecq V. Targeting the ubiquitin-proteasome pathway in breast cancer. Clin Breast Cancer 2004;5:148-57.
14. Dikic I. Mechanisms controlling EGF receptor endocytosis and degradation. Biochem Soc Trans 2003;31:1178-81.
15. Haglund K, Di Fiore PP, Dikic I. Distinct monoubiquitin signals in receptor endocytosis. Trends Biochem Sci 2003;28:598-603.
16. Moren A, Hellman U, Inada Y, Imamura T, Heldin CH, Moustakas A. Differential ubiquitination defines the functional status of the tumor suppressor Smad4. J Biol Chem 2003;278:33571-82.
17. Li M, Brooks CL, Wu-Baer F, Chen D, Baer R, Gu W. Mono- versus polyubiquitination: differential control of p53 fate by Mdm2. Science 2003;302:1972-5.
18. Grompe M, D'Andrea A. Fanconi anemia and DNA repair. Hum Mol Genet 2001;10:2253-9.
19. Chen ZJ. Ubiquitin signalling in the NF-κB pathway. Nat Cell Biol 2005;7:758-65.
20. Pickart CM. Back to the future with ubiquitin. Cell 2004;116:181-90.
21. Gao M, Labuda T, Xia Y, et al. Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch. Science 2004;306:271-5.
22. Yang C, Zhou W, Jeon MS, et al. Negative regulation of the E3 ubiquitin ligase itch via Fyn-mediated tyrosine phosphorylation. Mol Cell 2006;21:135-41.
23. Furukawa M, Andrews PS, Xiong Y. Assays for RING family ubiquitin ligases. Methods Mol Biol 2005;301:37-46.
24. Scheffner M, Huibregtse JM, Vierstra RD, Howley PM. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 1993;75:495-505.
25. Aravind L, Koonin EV. The U box is a modified RING finger: a common domain in ubiquitination. Curr Biol 2000;10:R132-34.
26. Vander Kooi CW, Ohi MD, Rosenberg JA, et al. The Prp19 U-box crystal structure suggests a common dimeric architecture for a class of oligomeric E3 ubiquitin ligases(,). Biochemistry 2006;45:121-30.
27. Hatakeyama S, Nakayama KI. U-box proteins as a new family of ubiquitin ligases. Biochem Biophys Res Commun 2003;302:635-45.
28. Xu W, Marcu M, Yuan X, Mimnaugh E, Patterson C, Neckers L. Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu. Proc Natl Acad Sci U S A 2002;99:12847-52.
29. Fan M, Park A, Nephew KP. CHIP (carboxy terminus of Hsc70-interacting protein) promotes basal and geldanamycin-induced degradation of estrogen receptor-α. Mol Endocrinol 2005;19:2901-14.
30. Lu Z, Xu S, Joazeiro C, Cobb MH, Hunter T. The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and mediates ubiquitination and degradation of ERK1/2. Mol Cell 2002;9:945-56.
31. Goto E, Ishido S, Sato Y, et al. c-MIR, a human E3 ubiquitin ligase, is a functional homolog of herpesvirus proteins MIR1 and MIR2 and has similar activity. J Biol Chem 2003;278:14657-68.
32. Uchida D, Hatakeyama S, Matsushima A, et al. AIRE functions as an E3 ubiquitin ligase. J Exp Med 2004;199:167-72.
33. Petroski MD, Deshaies RJ. Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol 2005;6:9-20.
34. 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.
35. Lindeman GJ, Wittlin S, Lada H, et al. SOCS1 deficiency results in accelerated mammary gland development and rescues lactation in prolactin receptor-deficient mice. Genes Dev 2001;15:1631-6.
36. Sutherland KD, Lindeman GJ, Choong DY, et al. Differential hypermethylation of SOCS genes in ovarian and breast carcinomas. Oncogene 2004;23:7726-33.
37. He Y, Zhang W, Zhang R, Zhang H, Min W. SOCS1 inhibits tumor necrosis factor-induced activation of ASK1-JNK inflammatory signaling by mediating ASK1 degradation. J Biol Chem 2006;281:5559-66.
38. Stogios PJ, Downs GS, Jauhal JJ, Nandra SK, Prive GG. Sequence and structural analysis of BTB domain proteins. Genome Biol 2005;6:R82.
39. Castro A, Bernis C, Vigneron S, Labbe JC, Lorca T. The anaphase-promoting complex: a key factor in the regulation of cell cycle. Oncogene 2005;24:314-25.
40. Gu J, Dubner R, Fornace AJ, Jr., Iadarola MJ. UREB1, a tyrosine phosphorylated nuclear protein, inhibits p53 transactivation. Oncogene 1995;11:2175-8.
41. 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.
42. Chen D, Kon N, Li M, Zhang W, Qin J, Gu W. ARF-BPI/Mule is a critical mediator of the ARF tumor suppressor. Cell 2005;121:1071-83.
43. Xie D, Jauch A, Miller CW, Bartram CR, Koeffler HP. Discovery of overexpressed genes and genetic alterations in breast cancer cells using a combination of suppression subtractive hybridization, multiplex FISH and comparative genomic hybridization. Int J Oncol 2002;21:499-507.
44. Chen C, Sun X, Guo P, et al. Human Kruppel-like factor 5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells. J Biol Chem 2005;280:41553-61.
45. Chen C, Sun X, Guo P, et al. Ubiquitin E3 ligase WWP1 as an Oncogenic factor in human prostate cancer. Oncogene in press 2006.
46. Seo SR, Lallemand F, Ferrand N, et al. The novel E3 ubiquitin ligase Tiu11 associates with TGIF to target Smad2 for degradation. EMBO J 2004;23:3780-92.
47. Moren A, Imamura T, Miyazono K, Heldin CH, Moustakas A. Degradation of the tumor suppressor Smad4 by WW and HECT domain ubiquitin ligases. J Biol Chem 2005;280:22115-23.
48. Komuro A, Imamura T, Saitoh M, et al. Negative regulation of transforming growth factor-β (TGF-β) signaling by WW domain-containing protein 1 (WWP1). Oncogene 2004;23:6914-23.
49. Zhang X, Srinivasan SV, Lingrel JB. WWP1-dependent ubiquitination and degradation of the lung Kruppel-like factor, KLF2. Biochem Biophys Res Commun 2004;316:139-48.
50. Wang F, Zhu Y, Huang Y, et al. Transcriptional repression of WEE1 by Kruppel-like factor 2 is involved in DNA damage-induced apoptosis. Oncogene 2005;24:3875-85
51. Chen C, Bhalala HV, Qiao H, Dong JT. A possible tumor suppressor role of the KLF5 transcription factor in human breast cancer. Oncogene 2002;21:6567-72.
52. Wick MJ, Blaine S, Van Putten V, Saavedra M, Nemenoff RA. Lung Kruppel-like factor (LKLF) is a transcriptional activator of the cytosolic phospholipase A2 alpha promoter. Biochem J 2005;387:239-46.
53. Bateman NW, Tan D, Pestell RG, Black JD, Black AR. Intestinal tumor progression is associated with altered function of KLF5. J Biol Chem 2004;279:12093-101.
54. Ingham RJ, Gish G, Pawson T. The Nedd4 family of E3 ubiquitin ligases: functional diversity within a common modular architecture. Oncogene 2004;23:1972-84.
55. Bueso-Ramos CE, Manshouri T, Haidar MA, et al. Abnormal expression of MDM-2 in breast carcinomas. Breast Cancer Res Treat 1996;37:179-88.
56. Jiang M, Shao ZM, Wu J, et al. p21/waf1/cip1 and mdm-2 expression in breast carcinoma patients as related to prognosis. Int J Cancer 1997;74:529-34.
57. Pinkas J, Naber SP, Butel JS, Medina D, Jerry DJ. Expression of MDM2 during mammary tumorigenesis. Int J Cancer 1999;81:292-8.
58. Bartel F, Taubert H, Harris LC. Alternative and aberrant splicing of MDM2 mRNA in human cancer. Cancer Cell 2002;2:9-15.
59. Lukas J, Gao DQ, Keshmeshian M, et al. Alternative and aberrant messenger RNA splicing of the mdm2 oncogene in invasive breast cancer. Cancer Res 2001;61:3212-9.
60. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 1992;69:1237-45.
61. Piette J, Neel H, Marechal V. Mdm2: keeping p53 under control. Oncogene 1997;15:1001-10.
62. Jones SN, Hancock AR, Vogel H, Donehower LA, Bradley A. Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis. Proc Natl Acad Sci U S A 1998;95:15608-12.
63. Fotouhi N, Graves B. Small molecule inhibitors of p53/MDM2 interaction. Curr Top Med Chem 2005;5:159-65.
64. Klein C, Vassilev LT. Targeting the p53-2 interaction to treat cancer. Br J Cancer 2004;91:1415-9.
65. Vassilev LT, Vu BT, Graves B, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004;303:844-8.
66. Issaeva N, Bozko P, Enge M, et al. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med 2004;10:1321-8.
67. Buolamwini JK, Addo J, Kamath S, Patil S, Mason D, Ores M. Small molecule antagonists of the MDM2 oncoprotein as anticancer agents. Curr Cancer Drug Targets 2005;5:57-68.
68. Urano T, Saito T, Tsukui T, et al. Efp targets 14-3-3 sigma for proteolysis and promotes breast tumour growth. Nature 2002;417:871-5.
69. Zou W, Zhang DE. The interferon-inducible ubiquitin-protein isopeptide ligase (E3) EFP also functions as an ISG15 E3 liease. J Biol Chem 2006;281:3989-94.
70. Suzuki T, Urano T, Tsukui T, et al. Estrogen-responsive finger protein as a new potential biomarker for breast cancer. Clin Cancer Res 2005;11:6148-54.
71. Horie K, Urano T, Inoue S. Efp as a new molecular target for breast cancer therapy. Anticancer Drugs 2003;14:1-2.
72. Wilkinson JC, Wilkinson AS, Scott FL, Csomos RA, Salvesen GS, Ducken CS. Neutralization of Smac/Diablo by inhibitors of apoptosis (IAPs). A caspase-independent mechanism for apoptotic inhibition. J Biol Chem 2004;279:51082-90.
73. Suzuki Y, Nakabayashi Y, Nakata K, Reed JC, Takahashi R. X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and -7 in distinct modes. J Biol Chem 2001;276:27058-63.
74. Morizane Y, Honda R, Fukami K, Yasuda H. X-linked inhibitor of apoptosis functions as ubiquitin ligase toward mature caspase-9 and cytosolic Smac DIABLO. J Biochem (Tokyo) 2005;137:125-32.
75. MacFarlane M, Merrison W, Bratton SB, Cohen GM. Proteasome-mediated degradation of Smac during apoptosis: XIAP promotes Smac ubiquitination in vitro. J Biol Chem 2002;277:36611-6.
76. Zhang Y, Wang Y, Gao W, et al. Transfer of siRNA against XIAP induces apoptosis and reduces tumor cells growth potential in human breast cancer in vitro and in vivo. Breast Cancer Res Treat 2005;96:267-77.
77. Lima RT, Martins LM, Guimaraes JE, Sambade C, Vasconcelos MH. Specific downregulation of bcl-2 and xIAP by RNAi enhances the effects of chemotherapeutic agents in MCF-7 human breast cancer cells. Cancer Gene Ther 2004;11:309-16.
78. Subramaniam V, Li H, Wong M, et al. The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf7 E3 ligase. Br J Cancer 2003;89:1538-44.
79. Li H, Seth A. An RNF11: Smurf2 complex mediates ubiquitination of the AMSH protein. Oncogene 2004;23:1801-8.
80. Azmi P, Seth A. RNF11 is a multifunctional modulator of growth factor receptor signalling and transcriptional regulation. Fur J Cancer 2005;41:2549-60.
81. Burger AM, Gao Y, Amemiya Y, et al. A novel RING-type ubiquitin ligase breast cancer-associated gene 2 correlates with outcome in invasive breast cancer. Cancer Res 2005;65:10401-12.
82. Forozan F, Mahlamaki EH, Monni O, et al. Comparative genomic hybridization analysis of 38 breast cancer cell lines: a basis for interpreting complementary DNA microarray data. Cancer Res 2000;60:4519-25.
83. 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.
84. Sonoda H, Inoue H, Ogawa K, Utsunomiya T, Masuda TA, Mori M. Significance of skp2 expression in primary breast cancer. Clin Cancer Res 2006;12:1215-20.
85. Carrano AC, Eytan E, Hershko A, Pagano M. SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nat Cell Biol 1999;1:193-9.
86. Yu ZK, Gervais JL, Zhang H. Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21(CIP1/WAF1) and cyclin D proteins. Proc Natl Acad Sci U S A 1998;95:11324-9.
87. 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.
88. Huang H, Regan KM, Wang F, et al. Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. Proc Natl Acad Sci U S A 2005;102:1649-54.
89. Ganoth D, Bornstein G, Ko TK, et al. The cell-cycle regulatory protein Cks1 is required for SCF(Skp2)-mediated ubiquitinylation of p27. Nat Cell Biol 2001;3:321-4.
90. Hao B, Zheng N, Schulman BA, et al. Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase. Mol Cell 2005;20:9-19.
91. Slotky M, Shapira M, Ben-Izhak O, et al. The expression of the ubiquitin ligase subunit Cks1 in human breast cancer. Breast Cancer Res 2005;7:R737-44.
92. Kudo Y, Guardavaccaro D, Santamaria PG, et al. Role of F-box protein βTrcp1 in mammary gland development and tumorigenesis. Mol Cell Biol 2004;24:8184-94.
93. Tang W, Li Y, Yu D, Thomas-Tikhonenko A, Spiegelman VS, Fuchs SY. Targeting β-transducin repeat-containing protein E3 ubiquitin ligase augments the effects of antitumor drugs on breast cancer cells. Cancer Res 2005;65:1904-8.
94. Winston JT, Strack P, Beer-Romero P, Chu CY, Elledge SJ, Harper JW. The SCFβ-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IκB-α and β-catenin and stimulates IκB-α ubiquitination in vitro. Genes Dev 1999;13:270-83.
95. Orian A, Gonen H, Bercovich B, et al. SCF(β)(-TrCP) ubiquitin ligase-mediated processing of NF-κB p105 requires phosphorylation of its C-terminus by IκB kinase. EMBO J 2000;19:2580-91.
96. Busino L, Donzelli M, Chiesa M, et al. Degradation of Cdc25A by β-TrCP during S phase and in response to DNA damage. Nature 2003;426:87-91.
97. Wan M, Tang Y, Tytler EM, et al. Smad4 protein stability is regulated by ubiquitin ligase SCF β-TrCP1. J Biol Chem 2004;279:14484-7.
98. Wan M, Huang J, Jhala NC, et al. SCF(β-TrCP1) controls Smad4 protein stability in pancreatic cancer cells. Am J Pathol 2005;166:1379-92.
99. Guardavaccaro D, Kudo Y, Boulaire J, et al. Control of meiotic and mitotic progression by the F box protein β-Trcp1 in vivo. Dev Cell 2003;4:799-812.
100. Chen LC, Manjeshwar S, Lu Y, et al. The human homologue for the Caenorhabditis elegans cul-4 gene is amplified and overexpressed in primary breast cancers. Cancer Res 1998;58:3677-83.
101. Nag A, Bagchi S, Raychaudhuri P. Cul4A physically associates with MDM2 and participates in the proteolysis of p53. Cancer Res 2004;64:8152-5.
102. Wertz IE, O'Rourke KM, Zhang Z, et al. Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. Science 2004;303:1371-4.
103. Li B, Ruiz JC, Chun KT. CUL-4A is critical for early embryonic development. Mol Cell Biol 2002;22:4997-5005.
104. 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.
105. Leng RP, Lin Y, Ma W, et al. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell 2003;112:779-91.
106. Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ. Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase. J Biol Chem 2002;277:22085-92.
107. Ishitobi M, Miyoshi Y, Hasegawa S, et al. Mutational analysis of BARD1 in familial breast cancer patients in Japan. Cancer Lett 2003;200:1-7.
108. 507Met in breast cancer predisposition. Eur J Hum Genet 2006;14:167-72.
109. Fabbro M, Schuechner S, Au WW, Henderson BR. BARD1 regulates BRCA1 apoptotic function by a mechanism involving nuclear retention. Exp Cell Res 2004;298:661-73.
110. Reinholz MM, An MW, Johnsen SA, et al. Differential gene expression of TGF β inducible early gene (TIEG), Smad7, Smad2 and Bard1 in normal and malignant breast tissue. Breast Cancer Res Treat 2004;86:75-88.
111. Wu JY, Vlastos AT, Pelte MF, et al. Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis. Int J Cancer 2006;118:1215-26.
112. Hashizume R, Fukuda M, Maeda I, et al. The RING heterodimer BRCA1-1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation. J Biol Chem 2001;276:14537-40.
113. Xia Y, Pao GM, Chen HW, Verma IM, Hunter T. Enhancement of BRCA1 E3 ubiquitin ligase activity through direct interaction with the BARD1 protein. J Biol Chem 2003;278:5255-63.
114. Hayami R, Sato K, Wu W, et al. Down-regulation of BRCA1-1 ubiquitin ligase by CDK2. Cancer Res 2005;65:6-10.
115. Dong Y, Hakimi MA, Chen X, et al. Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. Mol Cell 2003;12:1087-99.
116. Starita LM, Machida Y, Sankaran S, et al. BRCA1-dependent ubiquitination of gamma-tubulin regulates centrosome number. Mol Cell Biol 2004;24:8457-66.
117. Starita LM, Horwitz AA, Keogh MC, Ishioka C, Parvin JD, Chiba N. BRCA1/BARD1 ubiquitinate phosphorylated RNA polymerase II. J Biol Chem 2005;280:24498-505.
118. Matsuo K, Satoh S, Okabe H, et al. SIAH1 inactivation correlates with tumor progression in hepatocellular carcinomas. Genes Chromosomes Cancer 2003;36:283-91.
119. Bruzzoni-Giovanelli H, Faille A, Linares-Cruz G, et al. SIAH-1 inhibits cell growth by altering the mitotic process. Oncogene 1999;18:7101-9.
120. Germani A, Bruzzoni-Giovanelli H, Fellous A, Gisselbrecht S, Varin-Blank N, Calvo F. SIAH-1 interacts with -α-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis. Oncogene 2000;19:5997-6006.
121. Matsuzawa S, Li C, Ni CZ, Takayama S, Reed JC, Ely KR. Structural analysis of Siah1 and its interactions with Sigh-interacting protein (SIP). J Biol Chem 2003;278:1837-40.
122. Santelli E, Leone M, Li C, et al. Structural analysis of Siah1-Siah-interacting protein interactions and insights into the assembly of an E3 ligase multiprotein complex. J Biol Chem 2005;280:34278-87.
123. Fiucci G, Beaucourt S, Duflaut D, et al. Siah-1b is a direct transcriptional target of p53: identification of the functional p53 responsive element in the siah-1b promoter. Proc Natl Acad Sci U S A 2004;101:3510-5.
124. Tiedt R, Bartholdy BA, Matthias G, Newell JW, Matthias P. The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1. EMBO J 2001;20:4143-52.
125. Germani A, Prabel A, Mourah S, et al. SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway. Oncogene 2003;22:8845-51.
126. Susini L, Passer BJ, Amzallag-Elbaz N, et al. Siah-1 binds and regulates the function of Numb. Proc Natl Acad Sci U S A 2001;98:15067-72.
127. Cheung HW, Ching YP, Nicholls JM, et al. Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation. Mol Carcinog 2005;43:237-45.
128. 2/M checkpoint defects in breast cancer cells. Mol Carcinog 2004;39:26-33.
129. Yu X, Minter-Dykhouse K, Malureanu L, et al. Chfr is required for tumor suppression and Aurora A regulation. Nat Genet 2005;37:401-6.
130. 2 to M transition. J Cell Biol 2002;156:249-59.
131. Cesari R, Martin ES, Calin GA, et al. Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-27. Proc Natl Acad Sci U S A 2003;100:5956-61.
132. Picchio MC, Martin ES, Cesari R, et al. Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer. Clin Cancer Res 2004;10:2720-4.
133. Imai Y, Soda M, Takahashi R. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem 2000;275:35661-4.
134. Shimura H, Schlossmacher MG, Hattori N, et al. Ubiquitination of a new form of -α-synuclein by parkin from human brain: implications for Parkinson's disease. Science 2001;293:263-9.
135. Yang Y, Nishimura I, Imai Y, Takahashi R, Lu B. Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Neuron 2003;37:911-24.
136. Ko HS, von Coelln R, Sriram SR, et al. Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death. J Neurosci 2005;25:7968-78.
137. Ye X, Nalepa G, Welcker M, et al. Recognition of phosphodegron motifs in human cyclin E by the SCF(Fbw7) ubiquitin ligase. J Biol Chem 2004;279:50110-9.
138. Yada M, Hatakeyama S, Kamura T, et al. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J 2004;23:2116-25.
139. Wei W, Jin J, Schlisio S, Harper JW, Kaelin WG, Jr. 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.
140. Tetzlaff MT, Yu W, Li M, et al. Defective cardiovascular development and elevated cyclin E and Notch proteins in mice lacking the Fbw7 F-box protein. Proc Natl Acad Sci U S A 2004;101:3338-45.
141. Tsunematsu R, Nakayama K, Oike Y, et al. Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development. J Biol Chem 2004;279:9417-23.
142. Porter PL, Malone KE, Heagerty PJ, et al. Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients. Nat Med 1997;3:222-5.
143. Strohmaier H, Spruck CH, Kaiser P, Won KA, Sangfelt O, Reed SI. Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature 2001;413:316-22.
144. Harwell RM, Porter DC, Danes C, Keyomarsi K. Processing of cyclin E differs between normal and tumor breast cells. Cancer Res 2000;60:481-9.
145. Porter DC, Zhang N, Danes C, et al. Tumor-specific proteolytic processing of cyclin E generates hyperactive lower-molecular-weight forms. Mol Cell Biol 2001;21:6254-69.
146. Wang XD, Rosales JL, Magliocco A, Gnanakumar R, Lee KY. Cyclin E in breast tumors is cleaved into its low molecular weight forms by calpain. Oncogene 2003;22:769-74.
147. Hampton GM, Mannermaa A, Winqvist R, et al. Loss of heterozygosity in sporadic human breast carcinoma: a common region between 11q22 and 11q23.3. Cancer Res 1994;54:4586-9.
148. Fay MJ, Longo KA, Karathanasis GA, et al. Analysis of CUL-5 expression in breast epithelial cells, breast cancer cell lines, normal tissues and tumor tissues. Mol Cancer 2003;2:40.
149. Burnatowska-Hledin MA, Kossoris JB, Van Don CJ, et al. T47D breast cancer cell growth is inhibited by expression of VACM-1, a cul-5 gene. Biochem Biophys Res Commun 2004;319:817-25.
150. Wang X, DeFranco DB. Alternative effects of the ubiquitin-proteasome pathway on glucocorticoid receptor down-regulation and transactivation are mediated by CHIP, an E3 ligase. Mol Endocrinol 2005;19:1474-82.
151. Li L, Xin H, Xu X, et al. CHIP mediates degradation of Smad proteins and potentially regulates Smad-induced transcription. Mol Cell Biol 2004;24:856-64.
152. Xin H, Xu X, Li L, et al. CHIP controls the sensitivity of transforming growth factor-β signaling by modulating the basal level of Smad3 through ubiquitin-mediated degradation. J Biol Chem 2005;280:20842-50.
153. Imai Y, Soda M, Hatakeyama S, et al. CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity. Mol Cell 2002;10:55-67.
154. Lininger RA, Park WS, Man YG, et al. LOH at 16p13 is a novel chromosomal alteration detected in benign and malignant microdissected papillary neoplasms of the breast. Hum Pathol 1998;29:1113-8.
155. Nielsen NH, Amerlov C, Emdin SO, Landberg G. Cyclin E over-expression, a negative prognostic factor in breast cancer with strong correlation to oestrogen receptor status. Br J Cancer 1996;74:874-80.
156. Fredersdorf S, Burns J, Milne AM, et al. High level expression of p27(kip1) and cyclin D1 in some human breast cancer cells: inverse correlation between the expression of p27(kip1) and degree of malignancy in human breast and colorectal cancers. Proc Natl Acad Sci USA 1997;94:6380-5.
157. Grossman SR, Deato ME, Brignone C, et al. Polyubiquitination of p53 by a ubiquitin ligase activity of p300. Science 2003;300:342-4.
158. Rajendra R, Malegaonkar D, Pungaliya P, et al. Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. J Biol Chem 2004;279:36440-4.
159. Dornan D, Were I, Shimizu H, et al. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature 2004;429:86-92.
160. Duan W, Gao L, Druhan LJ, et al. Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer. J Natl Cancer Inst 2004;96:1718-21.
161. 2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A 1998;95:7987-92.
162. Salghetti SE, Kim SY, Tansey WP. Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc. EMBO J 1999;18:717-26.
163. Aberle H, Bauer A, Stappert J, Kispert A, Kemler R. β-catenin is a target for the ubiquitin-proteasome pathway. EMBO J 1997;16:3797-804.
164. Treier M, Staszewski LM, Bohmann D. Ubiquitin-dependent c-Jun degradation in vivo is mediated by the delta domain. Cell 1994;78:787-98.
165. Chen C, Sun X, Ran Q, et al. Ubiquitin-proteasome degradation of KLF5 transcription factor in cancer and untransformed epithelial cells. Oncogene 2005;24:3319-27.
166. Bendjennat M, Boulaire J, Jascur T, et al. UV irradiation triggers ubiquitin-dependent degradation of p21 (WAF1) to promote DNA repair. Cell 2003;114:599-610.
167. Morris JR, Solomon E. BRCA1: BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Hum Mol Genet 2004;13:807-17.
168. Yun J, Lee WH. Degradation of transcription repressor ZBRK1 through the ubiquitin-proteasome pathway relieves repression of Gadd45a upon DNA damage. Mol Cell Biol 2003;23:7305-14.
169. Garcia V, Dominguez G, Garcia JM, et al. Altered expression of the ZBRK1 gene in human breast carcinomas. J Pathol 2004;202:224-32.
170. Nishitani H, Sugimoto N, Roukos V, et al. Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-4, target human Cdt1 for proteolysis. EMBO J 2006;25:1126-36.
171. Hu J, Xiong Y. An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by the CuI4-1 ubiquitin ligase in response to DNA damage. J Biol Chem 2006;281:3753-6.
172. Matsuda N, Azuma K, Saijo M, et al. DDB2, the xeroderma pigmentosum group E gene product, is directly ubiquitylated by Cullin 4A-based ubiquitin ligase complex. DNA Repair (Amst) 2005;4:537-45.
173. Joazeiro CA, Wing SS, Huang H, Leverson JD, Hunter T, Liu YC. The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase. Science 1999;286:309-12.
174. Klapper LN, Waterman H, Sela M, Yarden Y. Tumor-inhibitory antibodies to HER-2/ErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of HER-2. Cancer Res 2000;60:3384-8.
175. Roy D, Calaf GM, Hande MP, Hei TK. Allelic imbalance at 11q23-24 chromosome associated with estrogen and radiation-induced breast cancer progression. Int J Oncol 2006;28:667-74.
176. Smit L, Borst J. The Cbl family of signal transduction molecules. Crit Rev Oncog 1997;8:359-79.
177. Ebisawa T, Fukuchi M, Murakami G, et al. Smurf1 interacts with transforming growth factor-β type I receptor through Smad7 and induces receptor degradation. J Biol Chem 2001;276:12477-80.
178. Kavsak P, Rasmussen RK, Causing CG, et al. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF β receptor for degradation. Mol Cell 2000;6:1365-75.
179. Li B, Dou QP. Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression. Proc Natl Acad Sci U S A 2000;97:3850-5.
180. Breitschopf K, Zeiher AM, Dimmeler S. Ubiquitin-mediated degradation of the proapoptotic active form of bid. A functional consequence on apoptosis induction. J Biol Chem 2000;275:21648-52.
181. Reginato MJ, Mills KR, Paulus JK, et al. Imegrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis. Nat Cell Biol 2003;5:733-40.
182. Warr MR, Acoca S, Liu Z, et al. BH3-ligand regulates access of MCL-1 to its E3 ligase. FEBS Lett 2005;579:5603-8.
183. Lehman NL, van de Rijn M, Jackson PK. Screening of tissue microarrays for ubiquitin proteasome system components in tumors. Methods Enzymol 2005;399:334-55.
184. Jin J, Ang XL, Shirogane T, Wade Harper J. Identification of substrates for f-box proteins. Methods Enzymol 2005:399:287-309.
185. Ayad NG, Rankin S, Ooi D, Rape M, Kirschner MW. Identification of ubiquitin ligase substrates by in vitro expression cloning. Methods Enzymol 2005;399:404-14.
186. Tang X, Orlicky S, Liu Q, Willems A, Sicheri F, Tyers M. Genome-wide surveys for phosphorylation-dependent substrates of SCF ubiquitin ligases. Methods Enzymol 2005;399:433-58.
187. Kus B, Gajadhar A, Stanger K, et al. A high throughput screen to identify substrates for the ubiquitin ligase Rsp5. J Biol Chem 2005;280:29470-8.
188. Schwikowski B, Uetz P, Fields S. A network of protein-protein interactions in yeast. Nat Biotechnol 2000;18:1257-61.
189. Giot L, Bader JS, Brouwer C, et al. A protein interaction map of Drosophila melanogaster. Science 2003;302:1727-36.
190. Li S, Armstrong CM, Bertin N, et al. A map of the interactome network of the metazoan C. elegans. Science 2004;303:540-3.
191. Rual JF, Venkatesan K, Hao T, et al. Towards a proteome-scale map of the human protein-protein interaction network. Nature 2005;437:1173-8.
192. Stelzl U, Worm U, Lalowski M, et al. A human protein-protein interaction network: a resource for annotating the proteome. Cell 2005;122:957-68.
193. Yang CH, Gonzalez-Angulo AM, Reuben JM, et al. Bortezomib (VELCADE(R)) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits. Ann Oncol 2006;17:813-7.
194. Colson K, Doss DS, Swift R, Tariman J, Thomas TE. Bortezomib, a newly approved proteasome inhibitor for the treatment of multiple myeloma: nursing implications. Clin J Oncol Nurs 2004;8:473-80.
195. Sun Y. Overview of approaches for screening for ubiquitin ligase inhibitors. Methods Enzymol 2005;399:654-63.
196. Davydov IV, Woods D, Safiran YJ, et al. Assay for ubiquitin ligase activity: high-throughput screen for inhibitors of HDM2. J Biomol Screen 2004;9:695-703.
197. Huang KS, Vassilev LT. High-throughput screening for inhibitors of the cksl-2 interaction. Methods Enzymol 2005;399:717-28.
198. Xu S, Patel P, Abbasian M, et al. In vitro SCF(β-Trcp1)-mediated IκBα ubiquitination assay for high-throughput screen. Methods Enzymol 2005;399:729-40.
199. Huang J, Sheung J, Dong G, Coquilla C, Daniel-Issakani S, Payan DG. High-throughput screening for inhibitors of the E3 ubiquitin ligase APC. Methods Enzymol 2005;399:740-54.
200. Garber K. Missing the target: ubiquitin ligase drugs stall. J Natl Cancer Inst 2005;97:166-7.
201. Nalepa G, Rolfe M, Harper JW. Drug discovery in the ubiquitin-proteasome system. Nat Rev Drug Discov 2006;5:596-613.
202. Michel JJ, Xiong Y. Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A. Cell Growth Differ 1998;9:435-49.
203. 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.
204. Kile BT, Schulman BA, Alexander WS, Nicola NA, Martin HM, Hilton DJ. The SOCS box: a tale of destruction and degradation. Trends Biochem Sci 2002;27:235-41.