The HECT Family of E3 Ubiquitin Ligases: Multiple Players in Cancer Development

Cancer Cell

Volumn 14, Issue 1, 2008, Pages 10-21

  Bernassola, Francesca ^a   Karin, Michael ^b   Ciechanover, Aaron ^c   Melino, Gerry ^a,d  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^d UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

HOMOLOGOUS TO E6 AP CARBOXYL TERMINUS TYPE E3 PROTEIN; HUWE1 PROTEIN; ITCH PROTEIN; PROTEIN E6; SMURF PROTEIN; UBIQUITIN; UBIQUITIN PROTEIN LIGASE; UBIQUITIN PROTEIN LIGASE E3; UBIQUITIN PROTEIN LIGASE NEDD4; WWP1 PROTEIN;

CARBOXY TERMINAL SEQUENCE; CARCINOGENESIS; CATALYSIS; ENZYME SPECIFICITY; HUMAN; NONHUMAN; PHYLOGENY; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN TARGETING; REVIEW; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE;

EID: 45849153870     PISSN: 15356108     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ccr.2008.06.001     Document Type: Review

References (106)

1. Adhikary S., Marinoni F., Hock A., Hulleman E., Popov N., Beier R., Bernard S., Quarto M., Capra M., Goettig S., et al. The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation. Cell 123 (2005) 409-421
2. Al-Hakim A.K., Zagorska A., Chapman L., Deak M., Peggie M., and Alessi D.R. Control of AMPK-related kinases by USP9X and atypical Lys29/Lys33-linked polyubiquitin chains. Biochem. J. 411 (2008) 249-260
3. Angers A., Ramjaun A.R., and McPherson P.S. The HECT domain ligase itch ubiquitinates endophilin and localizes to the trans-Golgi network and endosomal system. J. Biol. Chem. 279 (2004) 11471-11479
4. Bennett E.J., Shaler T.A., Woodman B., Ryu K.Y., Zaitseva T.S., Becker C.H., Bates G.P., Schulman H., and Kopito R.R. Global changes to the ubiquitin system in Huntington's disease. Nature 448 (2007) 704-708
5. Bergamaschi D., Gasco M., Hiller L., Sullivan A., Syed N., Trigiante G., Yulug I., Merlano M., Numico G., Comino A., et al. p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis. Cancer Cell 3 (2003) 387-402
6. Bernassola F., Salomoni P., Oberst A., Di Como C.J., Pagano M., Melino G., and Pandolfi P.P. Ubiquitin-dependent degradation of p73 is inhibited by PML. J. Exp. Med. 199 (2004) 1545-1557
7. Bonni S., Wang H.R., Causing C.G., Kavsak P., Stroschein S.L., Luo K., and Wrana J.L. TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation. Nat. Cell Biol. 3 (2001) 587-595
8. Cerutti J.M., Ebina K.N., Matsuo S.E., Martins L., Maciel R.M., and Kimura E.T. Expression of Smad4 and Smad7 in human thyroid follicular carcinoma cell lines. J. Endocrinol. Invest. 26 (2003) 516-521
9. Chastagner P., Israël A., and Brou C. Itch/AIP4 mediates Deltex degradation through the formation of K29-linked polyubiquitin chains. EMBO Rep. 7 (2006) 1147-1153
10. Chen C., Bhalala H.V., Qiao H., and Dong J.T. A possible tumor suppressor role of the KLF5 transcription factor in human breast cancer. Oncogene 21 (2002) 6567-6572
11. Chen C., Sun X., Guo P., Dong X.Y., Sethi P., Cheng X., Zhou J., Ling J., Simons J.W., Lingrel J.B., et al. Human Kruppel-like factor 5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells. J. Biol. Chem. 280 (2005) 41553-41561
12. Chen C., Sun X., Guo P., Dong X.Y., Sethi P., Zhou W., Zhou Z., Petros J., Frierson Jr. H.F., Vessella R.L., et al. Ubiquitin E3 ligase WWP1 as an oncogenic factor in human prostate cancer. Oncogene 26 (2007) 2386-2394
13. Chen C., Zhou Z., Ross J.S., Zhou W., and Dong J.T. The amplified WWP1 gene is a potential molecular target in breast cancer. Int. J. Cancer 121 (2007) 80-87
14. Chen D., Kon N., Li M., Zhang W., Qin J., and Gu W. ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor. Cell 121 (2005) 1071-1083
15. Ciechanover A. The ubiquitin-proteasome proteolytic pathway. Cell 79 (1994) 13-21
16. Ciechanover A. Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting. Cell Death Differ. 12 (2005) 1178-1190
17. Courbard J.R., Fiore F., Adélaïde J., Borg J.P., Birnbaum D., and Ollendorff V. Interaction between two ubiquitin-protein isopeptide ligases of different classes, CBLC and AIP4/ITCH. J. Biol. Chem. 277 (2002) 45267-45275
18. Cripps D., Thomas S.N., Jeng Y., Yang F., Davies P., and Yang A.J. Alzheimer disease-specific conformation of hyperphosphorylated paired helical filament-Tau is polyubiquitinated through Lys-48, Lys-11, and Lys-6 ubiquitin conjugation. J. Biol. Chem. 281 (2006) 10825-10838
19. Deng L., Wang C., Spencer E., Yang L., Braun A., You J., Slaughter C., Pickart C., and Chen Z.J. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103 (2000) 351-361
20. Diao J., Zhang Y., Huibregtse J.M., Zhou D., and Chen J. Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase. Nat. Struct. Mol. Biol. 15 (2008) 65-70
21. Di Fiore P.P., Polo S., and Hofmann K. When ubiquitin meets ubiquitin receptors: a signalling connection. Nat. Rev. Mol. Cell Biol. 4 (2003) 491-497
22. Dowdy S.C., Mariani A., Reinholz M.M., Keeney G.L., Spelsberg T.C., Podratz K.C., and Janknecht R. Overexpression of the TGF-beta antagonist Smad7 in endometrial cancer. Gynecol. Oncol. 96 (2005) 368-373
23. Dunn R., Klos D.A., Adler A.S., and Hicke L. The C2 domain of the Rsp5 ubiquitin ligase binds membrane phosphoinositides and directs ubiquitination of endosomal cargo. J. Cell Biol. 165 (2004) 135-144
24. Faiola F., Liu X., Lo S., Pan S., Zhang K., Lymar E., Farina A., and Martinez E. Dual regulation of c-Myc by p300 via acetylation-dependent control of Myc protein turnover and coactivation of Myc-induced transcription. Mol. Cell. Biol. 25 (2005) 10220-10234
25. Fang L., Lee S.W., and Aaronson S.A. Comparative analysis of p73 and p53 regulation and effector functions. J. Cell Biol. 147 (1999) 823-830
26. Flores E.R., Sengupta S., Miller J.B., Newman J.J., Bronson R., Crowley D., Yang A., McKeon F., and Jacks T. Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell 7 (2005) 363-373
27. Fouladkou F., Landry T., Kawabe H., Neeb A., Lu C., Brose N., Stambolic V., and Rotin D. The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization. Proc. Natl. Acad. Sci. USA. (2008) 10.1073/pnas.0803233105 Published online June 18, 2008
28. Fukuchi M., Fukai Y., Masuda N., Miyazaki T., Nakajima M., Sohda M., Manda R., Tsukada K., Kato H., and Kuwano H. High-level expression of the Smad ubiquitin ligase Smurf2 correlates with poor prognosis in patients with esophageal squamous cell carcinoma. Cancer Res. 62 (2002) 7162-7165
29. Gallagher E., Gao M., Liu Y.C., and Karin M. Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced conformational change. Proc. Natl. Acad. Sci. USA 103 (2006) 1717-1722
30. Gao M., Labuda T., Xia Y., Gallagher E., Fang D., Liu Y.C., and Karin M. Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch. Science 306 (2004) 271-275
31. Geetha T., Jiang J., and Wooten M.W. Lysine 63 polyubiquitination of the nerve growth factor receptor TrkA directs internalization and signaling. Mol. Cell 20 (2005) 301-312
32. Gressner O., Schilling T., Lorenz K., Schulze Schleithoff E., Koch A., Schulze-Bergkamen H., Lena A.M., Candi E., Terrinoni A., Catani M.V., et al. TAp63alpha induces apoptosis by activating signaling via death receptors and mitochondria. EMBO J. 24 (2005) 2458-2471
33. Gwizdek C., Hobeika M., Kus B., Ossareh-Nazari B., Dargemont C., and Rodriguez M.S. The mRNA nuclear export factor Hpr1 is regulated by Rsp5-mediated ubiquitylation. J. Biol. Chem. 280 (2005) 13401-13405
34. Haglund K., Sigismund S., Polo S., Szymkiewicz I., Di Fiore P.P., and Dikic I. Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation. Nat. Cell Biol. 5 (2003) 461-466
35. Hall J.R., Kow E., Nevis K.R., Lu C.K., Luce K.S., Zhong Q., and Cook J.G. Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA damage. Mol. Biol. Cell 18 (2007) 3340-3350
36. Hamilton M.H., Tcherepanova I., Huibregtse J.M., and McDonnell D.P. Nuclear import/export of hRPF1/Nedd4 regulates the ubiquitin-dependent degradation of its nuclear substrates. J. Biol. Chem. 276 (2001) 26324-26331
37. Hansen T.M., Rossi M., Roperch J.P., Ansell K., Simpson K., Taylor D., Mathon N., Knight R.A., and Melino G. Itch inhibition regulates chemosensitivity in vitro. Biochem. Biophys. Res. Commun. 361 (2007) 33-36
38. Harvey K.F., Dinudom A., Komwatana P., Jolliffe C.N., Day M.L., Parasivam G., Cook D.I., and Kumar S. All three WW domains of murine Nedd4 are involved in the regulation of epithelial sodium channels by intracellular Na+. J. Biol. Chem. 274 (1999) 12525-12530
39. Helliwell S.B., Losko S., Kaiser C.A., Henderson M.J., Russell A.J., Hird S., and Muñoz M. Components of a ubiquitin ligase complex specify polyubiquitination and intracellular trafficking of the general amino acid permease. J. Cell Biol. 153 (2001) 649-662
40. Herman-Bachinsky Y., Ryoo H.D., Ciechanover A., and Gonen H. Regulation of the Drosophila ubiquitin ligase DIAP1 is mediated via several distinct ubiquitin system pathways. Cell Death Differ. 14 (2007) 861-871
41. Hershko A. The ubiquitin system for protein degradation and some of its roles in the control of the cell division cycle. Cell Death Differ. 12 (2005) 1191-1197
42. Hershko A., and Ciechanover A. The ubiquitin system for protein degradation. Annu. Rev. Biochem. 67 (1998) 425-479
43. Hoeller D., Hecker C.M., Wagner S., Rogov V., Dötsch V., and Dikic I. E3-independent monoubiquitination of ubiquitin-binding proteins. Mol. Cell 26 (2007) 891-898
44. Huang L., Kinnucan E., Wang G., Beaudenon S., Howley P.M., Huibregtse J.M., and Pavletich N.P. Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade. Science 286 (1999) 1321-1326
45. Huibregtse J.M., Scheffner M., and Howley P.M. A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. EMBO J. 10 (1991) 4129-4135
46. Huibregtse J.M., Scheffner M., and Howley P.M. Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53. Mol. Cell. Biol. 13 (1993) 775-784
47. Huibregtse J.M., Scheffner M., and Howley P.M. Localization of the E6-AP regions that direct human papillomavirus E6 binding, association with p53, and ubiquitination of associated proteins. Mol. Cell. Biol. 13 (1993) 4918-4927
48. Huibregtse J.M., Scheffner M., Beaudenon S., and Howley P.M. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc. Natl. Acad. Sci. USA 92 (1995) 5249
49. Irwin M.S., Kondo K., Marin M.C., Cheng L.S., Hahn W.C., and Kaelin Jr. W.G. Chemosensitivity linked to p73 function. Cancer Cell 3 (2003) 403-410
50. Katz M., Shtiegman K., Tal-Or P., Yakir L., Mosesson Y., Harari D., Machluf Y., Asao H., Jovin T., Sugamura K., and Yarden Y. Ligand-independent degradation of epidermal growth factor receptor involves receptor ubiquitylation and Hgs, an adaptor whose ubiquitin-interacting motif targets ubiquitylation by Nedd4. Traffic 3 (2002) 740-751
51. Kavsak P., Rasmussen R.K., Causing C.G., Bonni S., Zhu H., Thomsen G.H., and Wrana J.L. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol. Cell 6 (2000) 1365-1375
52. Kumar S., Talis A.L., and Howley P.M. Identification of HHR23A as a substrate for E6-associated protein-mediated ubiquitination. J. Biol. Chem. 274 (1999) 18785-18792
53. Laine A., and Ronai Z. Regulation of p53 localization and transcription by the HECT domain E3 ligase WWP1. Oncogene 26 (2007) 1477-1483
54. Levkowitz G., Waterman H., Ettenberg S.A., Katz M., Tsygankov A.Y., Alroy I., Lavi S., Iwai K., Reiss Y., Ciechanover A., et al. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol. Cell 4 (1999) 1029-1040
55. Liu X., Yuan H., Fu B., Disbrow G.L., Apolinario T., Tomaic V., Kelley M.L., Baker C.C., Huibregtse J., and Schlegel R. The E6AP ubiquitin ligase is required for transactivation of the hTERT promoter by the human papillomavirus E6 oncoprotein. J. Biol. Chem. 280 (2005) 10807-10816
56. Liu Z., Oughtred R., and Wing S.S. Characterization of E3Histone, a novel testis ubiquitin protein ligase which ubiquitinates histones. Mol. Cell. Biol. 25 (2005) 2819-2831
57. Maillard I., and Pear W.S. Notch and cancer: best to avoid the ups and downs. Cancer Cell 3 (2003) 203-205
58. Marchese A., Raiborg C., Santini F., Keen J.H., Stenmark H., and Benovic J.L. The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. Dev. Cell 5 (2003) 709-802
59. Markowitz S., Wang J., Myeroff L., Parsons R., Sun L., Lutterbaugh J., Fan R.S., Zborowska E., Kinzler K.W., Vogelstein B., et al. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 268 (1995) 1336-1338
60. Martin-Serrano J., Eastman S.W., Chung W., and Bieniasz P.D. HECT ubiquitin ligases link viral and cellular PPXY motifs to the vacuolar protein-sorting pathway. J. Cell Biol. 168 (2005) 89-101
61. Maurice D., Pierreux C.E., Howell M., Wilentz R.E., Owen M.J., and Hill C.S. Loss of Smad4 function in pancreatic tumors: C-terminal truncation leads to decreased stability. J. Biol. Chem. 276 (2001) 43175-43181
62. McGill M.A., and McGlade C.J. Mammalian numb proteins promote Notch1 receptor ubiquitination and degradation of the Notch1 intracellular domain. J. Biol. Chem. 278 (2003) 23196-23203
63. Melino G., De Laurenzi V., and Vousden K.H. p73: Friend or foe in tumorigenesis. Nat. Rev. Cancer 2 (2002) 605-615
64. Melino G., Lu X., Gasco M., Crook T., and Knight R.A. Functional regulation of p73 and p63: development and cancer. Trends Biochem. Sci. 28 (2003) 663-670
65. Moren A., Imamura T., Miyazono K., Heldin C.H., and Moustakas A. Degradation of the tumor suppressor Smad4 by WW and HECT domain ubiquitin ligases. J. Biol. Chem. 280 (2005) 22115-22123
66. Mukhopadhyay D., and Riezman H. Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science 315 (2007) 201-205
67. Narisawa-Saito M., and Kiyono T. Basic mechanisms of high-risk human papillomavirus-induced carcinogenesis: roles of E6 and E7 proteins. Cancer Sci. 98 (2007) 1505-1511
68. Nicolas M., Wolfer A., Raj K., Kummer J.A., Mill P., van Noort M., Hui C.C., Clevers H., Dotto G.P., and Radtke F. Notch1 functions as a tumor suppressor in mouse skin. Nat. Genet. 33 (2003) 416-421
69. Nishikawa H., Ooka S., Sato K., Arima K., Okamoto J., Klevit R.E., Fukuda M., and Ohta T. Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase. J. Biol. Chem. 279 (2004) 3916-3924
70. Neumann S., Petfalski E., Brügger B., Grosshans H., Wieland F., Tollervey D., and Hurt E. Formation and nuclear export of tRNA, rRNA and mRNA is regulated by the ubiquitin ligase Rsp5p. EMBO Rep. 4 (2003) 1156-1162
71. Oberst A., Malatesta M., Aqeilan R.I., Rossi M., Salomoni P., Murillas R., Sharma P., Kuehn M.R., Oren M., Croce C.M., et al. The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch. Proc. Natl. Acad. Sci. USA 104 (2007) 11280-11285
72. Ogunjimi A.A., Briant D.J., Pece-Barbara N., Le Roy C., Di Guglielmo G.M., Kavsak P., Rasmussen R.K., Seet B.T., Sicheri F., and Wrana J.L. Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain. Mol. Cell 19 (2005) 297-308
73. Oliver P.M., Cao X., Worthen G.S., Shi P., Briones N., MacLeod M., White J., Kirby P., Kappler J., Marrack P., et al. Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation. Immunity 25 (2006) 929-940
74. Perry W.L., Hustad C.M., Swing D.A., O'Sullivan T.N., Jenkins N.A., and Copeland N.G. The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice. Nat. Genet. 18 (1998) 143-146
75. Polo S., Sigismund S., Faretta M., Guidi M., Capua M.R., Bossi G., Chen H., De Camilli P., and Di Fiore P.P. A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins. Nature 416 (2002) 451-455
76. Puig P., Capodieci P., Drobnjak M., Verbel D., Prives C., Cordon-Cardo C., and Di Como C.J. p73 Expression in human normal and tumor tissues: loss of p73alpha expression is associated with tumor progression in bladder cancer. Clin. Cancer Res. 9 (2003) 5642-5651
77. Qiu L., Joazeiro C., Fang N., Wang H.-Y., Elly C., Altman Y., Fang D., Hunter T., and Liu Y.-C. Recognition and ubiquitination of Notch by Itch, a hect-type E3 ubiquitin ligase. J. Biol. Chem. 275 (2000) 35734-35737
78. Rossi M., De Laurenzi V., Munarriz E., Green D.R., Liu Y.C., Vousden K.H., Cesareni G., and Melino G. The ubiquitin-protein ligase Itch regulates p73 stability. EMBO J. 24 (2005) 836-848
79. Rossi M., Aqeilan R.I., Neale M., Candi E., Salomoni P., Knight R.A., Croce C., and Melino G. The E3 ubiquitin ligase Itch controls the protein stability of p63. Proc. Natl. Acad. Sci. USA 103 (2006) 12753-12758
80. Scheffner M., and Staub O. HECT E3s and human disease. BMC Biochem. 8 (2007) S6
81. Scheffner M., Werness B.A., Huibregtse J.M., Levine A.J., and Howley P.M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63 (1990) 1129-1136
82. Scheffner M., Huibregtse J.M., and Howley P.M. Identification of a human ubiquitin-conjugating enzyme that mediates the E6-AP-dependent ubiquitination of p53. Proc. Natl. Acad. Sci. USA 91 (1994) 8797-8801
83. Schwarz S.E., Rosa J.L., and Scheffner M. Characterization of human hect domain family members and their interaction with UbcH5 and UbcH7. J. Biol. Chem. 273 (1998) 12148-12154
84. Shearwin-Whyatt L.M., Brown D.L., Wylie F.G., Stow J.L., and Kumar S. N4WBP5A (Ndfip2), a Nedd4-interacting protein, localizes to multivesicular bodies and the Golgi, and has a potential role in protein trafficking. J. Cell Sci. 117 (2004) 3679-3689
85. Shearwin-Whyatt L., Dalton H.E., Foot N., and Kumar S. Regulation of functional diversity within the Nedd4 family by accessory and adaptor proteins. Bioessays 28 (2006) 617-628
86. Shen W.H., Balajee A.S., Wang J., Wu H., Eng C., Pandolfi P.P., and Yin Y. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell 128 (2007) 157-170
87. Staub O., Gautschi I., Ishikawa T., Breitschopf K., Ciechanover A., Schild L., and Rotin D. Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination. EMBO J. 16 (1997) 6325-6336
88. Subramaniam V., Li H., Wong M., Kitching R., Attisano L., Wrana J., Zubovits J., Burger A.M., and Seth A. The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase. Br. J. Cancer 89 (2003) 1538-1544
89. Talis A.L., Huibregtse J.M., and Howley P.M. The role of E6AP in the regulation of p53 protein levels in human papillomavirus (HPV)-positive and HPV-negative cells. J. Biol. Chem. 273 (1998) 6439-6445
90. Trotman L.C., Wang X., Alimonti A., Chen Z., Teruya-Feldstein J., Yang H., Pavletich N.P., Carver B.S., Cordon-Cardo C., Erdjument-Bromage H., et al. Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell 128 (2007) 141-156
91. Urist M.J., Di Como C.J., Lu M.L., Charytonowicz E., Verbel D., Crum C.P., Ince T.A., McKeon F.D., and Cordon-Cardo C. Loss of p63 expression is associated with tumor progression in bladder cancer. Am. J. Pathol. 161 (2002) 1199-1206
92. Verdecia M.A., Joazeiro C.A., Wells N.J., Ferrer J.L., Bowman M.E., Hunter T., and Noel J.P. Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase. Mol. Cell 11 (2003) 249-259
93. Vervoorts J., Luscher-Firzlaff J.M., Rottmann S., Lilischkis R., Walsemann G., Dohmann K., Austen M., and Luscher B. Stimulation of c-MYC transcriptional activity and acetylation by recruitment of the cofactor CBP. EMBO Rep. 4 (2003) 484-490
94. Vervoorts J., Luscher-Firzlaff J., and Luscher B. The ins and outs of MYC regulation by posttranslational mechanisms. J. Biol. Chem. 281 (2006) 34725-34729
95. Voorhees P.M., and Orlowski R.Z. The proteasome and proteasome inhibitors in cancer therapy. Annu. Rev. Pharmacol. Toxicol. 46 (2006) 189-213
96. Wang C., Deng L., Hong M., Akkaraju G.R., Inoue J., and Chen Z.J. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412 (2001) 346-351
97. Wang X., Trotman L.C., Koppie T., Alimonti A., Chen Z., Gao Z., Wang J., Erdjument-Bromage H., Tempst P., Cordon-Cardo C., et al. NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell 128 (2007) 129-139
98. Wegierski T., Hill K., Schaefer M., and Walz G. The HECT ubiquitin ligase AIP4 regulates the cell surface expression of select TRP channels. EMBO J. 25 (2006) 5659-5669
99. Wiesner S., Ogunjimi A.A., Wang H.R., Rotin D., Sicheri F., Wrana J.L., and Forman-Kay J.D. Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain. Cell 130 (2007) 651-662
100. Xu J., and Attisano L. Mutations in the tumor suppressors Smad2 and Smad4 inactivate transforming growth factor beta signaling by targeting Smads to the ubiquitin-proteasome pathway. Proc. Natl. Acad. Sci. USA 97 (2000) 4820-4825
101. Yang Y., Ludwig R.L., Jensen J.P., Pierre S.A., Medaglia M.V., Davydov I.V., Safiran Y.J., Oberoi P., Kenten J.H., Phillips A.C., et al. Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell 7 (2005) 547-559
102. Yoon S.Y., Lee Y., Kim J.H., Chung A.S., Joo J.H., Kim C.N., Kim N.S., Choe I.S., and Kim J.W. 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. 326 (2005) 7-17
103. Zhang Y., Chang C., Gehling D.J., Hemmati-Brivanlou A., and Derynck R. Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase. Proc. Natl. Acad. Sci. USA 98 (2001) 974-979
104. Zhao X., Julian J.I.-T., Guardavaccaro D., Jiang R., Pagano M., Guillemot F., Iavarone A., and Lasorella A. The HECT-domain ubiquitin ligase Ureb1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein. Nat. Cell Biol. (2008) 10.1038/ncb1727
105. Zhong Q., Gao W., Du F., and Wang X. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell 121 (2005) 1085-1095
106. Zhu H., Kavsak P., Abdollah S., Wrana J.L., and Thomsen G.H. A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature 400 (1999) 687-693