Screening for E3-Ubiquitin ligase inhibitors: Challenges and opportunities

Oncotarget

Volumn 5, Issue 18, 2014, Pages 7988-8013

  Landré, Vivien ^a   Rotblat, Barak ^a   Melino, Sonia ^b   Bernassola, Francesca ^b   Melino, Gerry ^a,b  

^a MEDICAL RESEARCH COUNCIL   (United Kingdom)

^b UNIVERSITY OF ROME TOR VERGATA   (Italy)

Author keywords

Clomipramine; HECT; High throughput screening; ITCH; P63; P73; Small molecular inhibitor; Therapeutics

Indexed keywords

BORTEZOMIB; CARFILZOMIB; CLOMIPRAMINE; DEUBIQUITINASE; GDC 0152; HL 198; INHIBITOR OF APOPTOSIS PROTEIN; LIGASE INHIBITOR; NSC 681152; NSC 689857; NSC 697923; PEVONEDISTAT; PROTEASOME; PROTEIN ITCH; PROTEIN MDM2; PROTEIN P53; PROTEIN P63; PROTEIN P73; S PHASE KINASE ASSOCIATED PROTEIN 2; SM 406; TDP 521252; TDP 665759; TRANSCRIPTION FACTOR; UBIQUITIN; UBIQUITIN PROTEIN LIGASE; UBIQUITIN PROTEIN LIGASE E2 INHIBITOR; UBIQUITIN PROTEIN LIGASE E3 INHIBITOR; UBIQUITIN PROTEIN LIGASE NEDD4; UNCLASSIFIED DRUG; UNINDEXED DRUG; [2 (4 TERT BUTYL 2 ETHOXYPHENYL) 4,5 BIS(4 CHLOROPHENYL) 4,5 DIHYDRO 4,5 DIMETHYL 1H IMIDAZOL 1 YL][4 [3 (METHYLSULFONYL)PROPYL] 1 PIPERAZINYL]METHANONE; PROTEASOME INHIBITOR;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ANEMIA; APOPTOSIS; ARTICLE; AUTISM; BONE MARROW SUPPRESSION; BREAST CANCER; CANCER CELL; CANCER INHIBITION; CARDIOTOXICITY; CELL CYCLE ARREST; CELL DEATH; CELL PROLIFERATION; CELLULAR DISTRIBUTION; COLORECTAL CANCER; COMPUTER MODEL; DEGENERATIVE DISEASE; DEVELOPMENTAL DISORDER; DNA DAMAGE; DNA REPAIR; DRUG SCREENING; DRUG STRUCTURE; DRUG TARGETING; HAPPY PUPPET SYNDROME; HEMOCHROMATOSIS; HUMAN; HUNTINGTON CHOREA; HYPERTENSION; IN VITRO STUDY; INFLAMMATORY DISEASE; LARGE CELL LYMPHOMA; LIDDLE SYNDROME; LIPOSARCOMA; MANTLE CELL LYMPHOMA; METASTASIS; MULTIPLE MYELOMA; NEPHROBLASTOMA; NEUROBLASTOMA; NEUTROPENIA; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PATHOGENESIS; PERIPHERAL NEUROPATHY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROSTATE CANCER; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN MODIFICATION; PROTEIN PROTEIN INTERACTION; THROMBOCYTOPENIA; TUBEROUS SCLEROSIS; UBIQUITINATION; UNSPECIFIED SIDE EFFECT; UTERINE CERVIX CANCER; VASCULAR DISEASE; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG DEVELOPMENT; DRUG EFFECTS; METABOLISM; MOLECULARLY TARGETED THERAPY; SIGNAL TRANSDUCTION;

ANIMALS; DRUG DISCOVERY; HUMANS; MOLECULAR TARGETED THERAPY; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEASOME INHIBITORS; SIGNAL TRANSDUCTION; UBIQUITIN-PROTEIN LIGASES; UBIQUITINATION;

EID: 84907831745     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.2431     Document Type: Article

References (281)

1. Melino G, Knight RA and Nicotera P. How many ways to die? How many different models of cell death? Cell death and differentiation. 2005; 12 Suppl 2:1457-1462.
2. Muller M, Schleithoff ES, Stremmel W, Melino G, Krammer PH and Schilling T. One, two, three-p53, p63, p73 and chemosensitivity. Drug resistance updates: reviews and commentaries in antimicrobial and anticancer chemotherapy. 2006; 9(6):288-306.
3. 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 and differentiation. 2005; 12(9):1178-1190.
4. Hershko A. The ubiquitin system for protein degradation and some of its roles in the control of the cell division cycle. Cell death and differentiation. 2005; 12(9):1191-1197.
5. Rose I. Ubiquitin at Fox Chase. Cell death and differentiation. 2005; 12(9):1198-1201.
6. Severe N, Dieudonne FX and Marie PJ. E3 ubiquitin ligase-mediated regulation of bone formation and tumorigenesis. Cell death & disease. 2013; 4.
7. Smalle J and Vierstra RD. The ubiquitin 26S proteasome proteolytic pathway. Annual review of plant biology. 2004; 55:555-590.
8. Bernassola F, Ciechanover A and Melino G. The ubiquitin proteasome system and its involvement in cell death pathways. Cell death and differentiation. 2010; 17(1):1-3.
9. Shi D and Grossman SR. Ubiquitin becomes ubiquitous in cancer: emerging roles of ubiquitin ligases and deubiquitinases in tumorigenesis and as therapeutic targets. Cancer biology & therapy. 2010; 10(8):737-747.
10. Bernassola F, Karin M, Ciechanover A and Melino G. The HECT family of E3 ubiquitin ligases: multiple players in cancer development. Cancer cell. 2008; 14(1):10-21.
11. Schwartz AL and Ciechanover A. Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology. Annual review of pharmacology and toxicology. 2009; 49:73-96.
12. Halaby MJ, Hakem R and Hakem A. Pirh2: an E3 ligase with central roles in the regulation of cell cycle, DNA damage response, and differentiation. Cell cycle (Georgetown, Tex). 2013; 12(17):2733-2737.
13. Navon A and Ciechanover A. The 26 S proteasome: from basic mechanisms to drug targeting. The Journal of biological chemistry. 2009; 284(49):33713-33718.
14. Cohen P and Tcherpakov M. Will the ubiquitin system furnish as many drug targets as protein kinases? Cell. 2010; 143(5):686-693.
15. Davare MA, Saborowski A, Eide CA, Tognon C, Smith RL, Elferich J, Agarwal A, Tyner JW, Shinde UP, Lowe SW and Druker BJ. Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins. Proceedings of the National Academy of Sciences of the United States of America. 2013; 110(48):19519-19524.
16. Orlowski RZ, Stinchcombe TE, Mitchell BS, Shea TC, Baldwin AS, Stahl S, Adams J, Esseltine DL, Elliott PJ, Pien CS, Guerciolini R, Anderson JK, Depcik-Smith ND, Bhagat R, Lehman MJ, Novick SC, et al. Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2002; 20(22):4420-4427.
17. Haas AL and Rose IA. The mechanism of ubiquitin activating enzyme. A kinetic and equilibrium analysis. The Journal of biological chemistry. 1982; 257(17):10329-10337.
18. Haas AL, Warms JV, Hershko A and Rose IA. Ubiquitin-activating enzyme. Mechanism and role in protein-ubiquitin conjugation. The Journal of biological chemistry. 1982; 257(5):2543-2548.
19. Hershko A and Ciechanover A. The ubiquitin system. Annual review of biochemistry. 1998; 67:425-479.
20. Pickart CM and Eddins MJ. Ubiquitin: structures, functions, mechanisms. Biochimica et biophysica acta. 2004; 1695(1-3):55-72.
21. Nuber U, Schwarz S, Kaiser P, Schneider R and Scheffner M. Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5. The Journal of biological chemistry. 1996; 271(5):2795-2800.
22. Huibregtse JM, Scheffner M, Beaudenon S and Howley PM. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proceedings of the National Academy of Sciences of the United States of America. 1995; 92(7):2563-2567.
23. Li Y, Kong Y, Zhou Z, Chen H, Wang Z, Hsieh YC, Zhao D, Zhi X, Huang J, Zhang J, Li H and Chen C. The HECTD3 E3 ubiquitin ligase facilitates cancer cell survival by promoting K63-linked polyubiquitination of caspase-8. Cell death & disease. 2013; 4:e935.
24. Zhao Y, Xiong X, Jia L and Sun Y. Targeting Cullin-RING ligases by MLN4924 induces autophagy via modulating the HIF1-REDD1-TSC1-mTORC1-DEPTOR axis. Cell death & disease. 2012; 3:e386.
25. Li Y, Kong Y, Zhou Z, Chen H, Wang Z, Hsieh YC, Zhao D, Zhi X, Huang J, Zhang J, Li H and Chen C. The HECTD3 E3 ubiquitin ligase facilitates cancer cell survival by promoting K63-linked polyubiquitination of caspase-8. Cell death & disease. 2013; 4.
26. Mevissen TE, Hospenthal MK, Geurink PP, Elliott PR, Akutsu M, Arnaudo N, Ekkebus R, Kulathu Y, Wauer T, El Oualid F, Freund SM, Ovaa H and Komander D. OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis. Cell. 2013; 154(1):169-184.
27. Faronato M, Patel V, Darling S, Dearden L, Clague MJ, Urbe S and Coulson JM. The deubiquitylase USP15 stabilizes newly synthesized REST and rescues its expression at mitotic exit. Cell cycle (Georgetown, Tex). 2013; 12(12):1964-1977.
28. Yang CS, Sinenko SA, Thomenius MJ, Robeson AC, Freel CD, Horn SR and Kornbluth S. The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis. Cell death and differentiation. 2014; 21(4):604-611.
29. Thrower JS, Hoffman L, Rechsteiner M and Pickart CM. Recognition of the polyubiquitin proteolytic signal. The EMBO journal. 2000; 19(1):94-102.
30. Suryadinata R, Holien JK, Yang G, Parker MW, Papaleo E and Sarcevic B. Molecular and structural insight into lysine selection on substrate and ubiquitin lysine 48 by the ubiquitin-conjugating enzyme Cdc34. Cell cycle (Georgetown, Tex). 2013; 12(11):1732-1744.
31. Kirisako T, Kamei K, Murata S, Kato M, Fukumoto H, Kanie M, Sano S, Tokunaga F, Tanaka K and Iwai K. A ubiquitin ligase complex assembles linear polyubiquitin chains. The EMBO journal. 2006; 25(20):4877-4887.
32. Gerlach B, Cordier SM, Schmukle AC, Emmerich CH, Rieser E, Haas TL, Webb AI, Rickard JA, Anderton H, Wong WW, Nachbur U, Gangoda L, Warnken U, Purcell AW, Silke J and Walczak H. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature. 2011; 471(7340):591-596.
33. Ben-Saadon R, Zaaroor D, Ziv T and Ciechanover A. The polycomb protein Ring1B generates self atypical mixed ubiquitin chains required for its in vitro histone H2A ligase activity. Molecular cell. 2006; 24(5):701-711.
34. Komander D and Rape M. The ubiquitin code. Annual review of biochemistry. 2012; 81:203-229.
35. Xu P, Duong DM, Seyfried NT, Cheng D, Xie Y, Robert J, Rush J, Hochstrasser M, Finley D and Peng J. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell. 2009; 137(1):133-145.
36. Bedford L, Layfield R, Mayer RJ, Peng J and Xu P. Diverse polyubiquitin chains accumulate following 26S proteasomal dysfunction in mammalian neurones. Neuroscience letters. 2011; 491(1):44-47.
37. Kravtsova-Ivantsiv Y and Ciechanover A. Non-canonical ubiquitin-based signals for proteasomal degradation. Journal of cell science. 2012; 125(Pt 3):539-548.
38. Jacobson AD, Zhang NY, Xu P, Han KJ, Noone S, Peng J and Liu CW. The lysine 48 and lysine 63 ubiquitin conjugates are processed differently by the 26 s proteasome. The Journal of biological chemistry. 2009; 284(51):35485-35494.
39. Strieter ER and Korasick DA. Unraveling the complexity of ubiquitin signaling. ACS chemical biology. 2012; 7(1):52-63.
40. Lauwers E, Erpapazoglou Z, Haguenauer-Tsapis R and Andre B. The ubiquitin code of yeast permease trafficking. Trends in cell biology. 2010; 20(4):196-204.
41. Lauwers E, Jacob C and Andre B. K63-linked ubiquitin chains as a specific signal for protein sorting into the multivesicular body pathway. The Journal of cell biology. 2009; 185(3):493-502.
42. Shih SC, Sloper-Mould KE and Hicke L. Monoubiquitin carries a novel internalization signal that is appended to activated receptors. The EMBO journal. 2000; 19(2):187-198.
43. Terrell J, Shih S, Dunn R and Hicke L. A function for monoubiquitination in the internalization of a G protein-coupled receptor. Molecular cell. 1998; 1(2):193-202.
44. Nakatsu F, Sakuma M, Matsuo Y, Arase H, Yamasaki S, Nakamura N, Saito T and Ohno H. A Di-leucine signal in the ubiquitin moiety. Possible involvement in ubiquitination-mediated endocytosis. The Journal of biological chemistry. 2000; 275(34):26213-26219.
45. Haglund K, Sigismund S, Polo S, Szymkiewicz I, Di Fiore PP and Dikic I. Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation. Nature cell biology. 2003; 5(5):461-466.
46. Mosesson Y, Shtiegman K, Katz M, Zwang Y, Vereb G, Szollosi J and Yarden Y. Endocytosis of receptor tyrosine kinases is driven by monoubiquitylation, not polyubiquitylation. The Journal of biological chemistry. 2003; 278(24):21323-21326.
47. Kirkin V, McEwan DG, Novak I and Dikic I. A role for ubiquitin in selective autophagy. Molecular cell. 2009; 34(3):259-269.
48. Shaid S, Brandts CH, Serve H and Dikic I. Ubiquitination and selective autophagy. Cell death and differentiation. 2013; 20(1):21-30.
49. Pal P, Lochab S, Kanaujiya JK, Kapoor I, Sanyal S, Behre G and Trivedi AK. E6AP, an E3 ubiquitin ligase negatively regulates granulopoiesis by targeting transcription factor C/EBP alpha for ubiquitin-mediated proteasome degradation. Cell death & disease. 2013; 4.
50. Alkalay I, Yaron A, Hatzubai A, Orian A, Ciechanover A and Ben-Neriah Y. Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway. Proceedings of the National Academy of Sciences of the United States of America. 1995; 92(23):10599-10603.
51. Hayden MS and Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008; 132(3):344-362.
52. Kaelin WG, Jr. The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer. Nature reviews Cancer. 2008; 8(11):865-873.
53. Tian YM, Yeoh KK, Lee MK, Eriksson T, Kessler BM, Kramer HB, Edelmann MJ, Willam C, Pugh CW, Schofield CJ and Ratcliffe PJ. Differential sensitivity of hypoxia inducible factor hydroxylation sites to hypoxia and hydroxylase inhibitors. The Journal of biological chemistry. 2011; 286(15):13041-13051.
54. Rotili D, Altun M, Kawamura A, Wolf A, Fischer R, Leung IK, Mackeen MM, Tian YM, Ratcliffe PJ, Mai A, Kessler BM and Schofield CJ. A photoreactive small-molecule probe for 2-oxoglutarate oxygenases. Chemistry & biology. 2011; 18(5):642-654.
55. Leveillard T, Gorry P, Niederreither K and Wasylyk B. MDM2 expression during mouse embryogenesis and the requirement of p53. Mechanisms of development. 1998; 74(1-2):189-193.
56. Montes de Oca Luna R, Wagner DS and Lozano G. Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature. 1995; 378(6553):203-206.
57. Parant J, Chavez-Reyes A, Little NA, Yan W, Reinke V, Jochemsen AG and Lozano G. Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53. Nature genetics. 2001; 29(1):92-95.
58. Love IM and Grossman SR. It Takes 15 to Tango: Making Sense of the Many Ubiquitin Ligases of p53. Genes & cancer. 2012; 3(3-4):249-263.
59. Melino G, Gallagher E, Aqeilan RI, Knight R, Peschiaroli A, Rossi M, Scialpi F, Malatesta M, Zocchi L, Browne G, Ciechanover A and Bernassola F. Itch: a HECT-type E3 ligase regulating immunity, skin and cancer. Cell death and differentiation. 2008; 15(7):1103-1112.
60. Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C and McKeon F. p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature. 1999; 398(6729):714-718.
61. Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR and Bradley A. p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature. 1999; 398(6729):708-713.
62. Agostini M, Tucci P, Killick R, Candi E, Sayan BS, Rivetti di Val Cervo P, Nicotera P, McKeon F, Knight RA, Mak TW and Melino G. Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets. Proceedings of the National Academy of Sciences of the United States of America. 2011; 108(52):21093-21098.
63. Rossi M, Munarriz ER, Bartesaghi S, Milanese M, Dinsdale D, Guerra-Martin MA, Bampton ET, Glynn P, Bonanno G, Knight RA, Nicotera P and Melino G. Desmethylclomipramine induces the accumulation of autophagy markers by blocking autophagic flux. Journal of cell science. 2009; 122(Pt 18):3330-3339.
64. Bellomaria A, Barbato G, Melino G, Paci M and Melino S. Recognition of p63 by the E3 ligase ITCH: Effect of an ectodermal dysplasia mutant. Cell cycle (Georgetown, Tex). 2010; 9(18):3730-3739.
65. Bellomaria A, Barbato G, Melino G, Paci M and Melino S. Recognition mechanism of p63 by the E3 ligase Itch: novel strategy in the study and inhibition of this interaction. Cell cycle (Georgetown, Tex). 2012; 11(19):3638-3648.
66. Melino G, Knight RA and Cesareni G. Degradation of p63 by Itch. Cell cycle (Georgetown, Tex). 2006; 5(16):1735-1739.
67. Rossi M, Aqeilan RI, Neale M, Candi E, Salomoni P, Knight RA, Croce CM and Melino G. The E3 ubiquitin ligase Itch controls the protein stability of p63. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103(34):12753-12758.
68. Rossi M, De Laurenzi V, Munarriz E, Green DR, Liu YC, Vousden KH, Cesareni G and Melino G. The ubiquitin-protein ligase Itch regulates p73 stability. The EMBO journal. 2005; 24(4):836-848.
69. Eldridge AG and O'Brien T. Therapeutic strategies within the ubiquitin proteasome system. Cell death and differentiation. 2010; 17(1):4-13.
70. Levy D, Adamovich Y, Reuven N and Shaul Y. The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73. Cell death and differentiation. 2007; 14(4):743-751.
71. Levy D, Reuven N and Shaul Y. A regulatory circuit controlling Itch-mediated p73 degradation by Runx. The Journal of biological chemistry. 2008; 283(41):27462-27468.
72. Oberst A, Malatesta M, Aqeilan RI, Rossi M, Salomoni P, Murillas R, Sharma P, Kuehn MR, Oren M, Croce CM, Bernassola F and Melino G. The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(27):11280-11285.
73. Aqeilan RI, Pekarsky Y, Herrero JJ, Palamarchuk A, Letofsky J, Druck T, Trapasso F, Han SY, Melino G, Huebner K and Croce CM. Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. Proceedings of the National Academy of Sciences of the United States of America. 2004; 101(13):4401-4406.
74. Salah Z, Bar-Mag T, Kohn Y, Pichiorri F, Palumbo T, Melino G and Aqeilan RI. Tumor suppressor WWOX binds to DeltaNp63alpha and sensitizes cancer cells to chemotherapy. Cell death & disease. 2013; 4:e480.
75. Peschiaroli A, Scialpi F, Bernassola F, El Sherbini E and Melino G. The E3 ubiquitin ligase WWP1 regulates Delta Np63-dependent transcription through Lys63 linkages. Biochem Bioph Res Co. 2010; 402(2):425-430.
76. Li C, Chang DL, Yang Z, Qi J, Liu R, He H, Li D and Xiao ZX. Pin1 modulates p63alpha protein stability in regulation of cell survival, proliferation and tumor formation. Cell death & disease. 2013; 4:e943.
77. Sayan BS, Yang AL, Conforti F, Tucci P, Piro MC, Browne GJ, Agostini M, Bernardini S, Knight RA, Mak TW and Melino G. Differential control of TAp73 and DeltaNp73 protein stability by the ring finger ubiquitin ligase PIR2. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107(29):12877-12882.
78. Peschiaroli A, Scialpi F, Bernassola F, Pagano M and Melino G. The F-box protein FBXO45 promotes the proteasome-dependent degradation of p73. Oncogene. 2009; 28(35):3157-3166.
79. Gonzalez-Cano L, Hillje AL, Fuertes-Alvarez S, Marques MM, Blanch A, Ian RW, Irwin MS, Schwamborn JC and Marin MC. Regulatory feedback loop between TP73 and TRIM32. Cell death & disease. 2013; 4.
80. Chen ZJ and Sun LJ. Nonproteolytic functions of ubiquitin in cell signaling. Molecular cell. 2009; 33(3):275-286.
81. Dikic I, Wakatsuki S and Walters KJ. Ubiquitin-binding domains-from structures to functions. Nature reviews Molecular cell biology. 2009; 10(10):659-671.
82. Hochstrasser M. Origin and function of ubiquitin-like proteins. Nature. 2009; 458(7237):422-429.
83. Baker R, Lewis SM, Sasaki AT, Wilkerson EM, Locasale JW, Cantley LC, Kuhlman B, Dohlman HG and Campbell SL. Site-specific monoubiquitination activates Ras by impeding GTPase-activating protein function. Nature structural & molecular biology. 2013; 20(1):46-52.
84. Chernorudskiy AL and Gainullin MR. Ubiquitin system: direct effects join the signaling. Science signaling. 2013; 6(280):pe22.
85. Sagar GD, Gereben B, Callebaut I, Mornon JP, Zeold A, da Silva WS, Luongo C, Dentice M, Tente SM, Freitas BC, Harney JW, Zavacki AM and Bianco AC. Ubiquitination-induced conformational change within the deiodinase dimer is a switch regulating enzyme activity. Molecular and cellular biology. 2007; 27(13):4774-4783.
86. Chen BB and Mallampalli RK. Masking of a nuclear signal motif by monoubiquitination leads to mislocalization and degradation of the regulatory enzyme cytidylyltransferase. Molecular and cellular biology. 2009; 29(11):3062-3075.
87. Lee JT and Gu W. The multiple levels of regulation by p53 ubiquitination. Cell death and differentiation. 2010; 17(1):86-92.
88. Green DR and Kroemer G. Cytoplasmic functions of the tumour suppressor p53. Nature. 2009; 458(7242):1127-1130.
89. Hansen TM, Rossi M, Roperch JP, Ansell K, Simpson K, Taylor D, Mathon N, Knight RA and Melino G. Itch inhibition regulates chemosensitivity in vitro. Biochem Biophys Res Commun. 2007; 361(1):33-36.
90. Fukuchi M, Imamura T, Chiba T, Ebisawa T, Kawabata M, Tanaka K and Miyazono K. Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of ROC1 and associated proteins. Molecular biology of the cell. 2001; 12(5):1431-1443.
91. Trotman LC, Wang X, Alimonti A, Chen Z, Teruya-Feldstein J, Yang H, Pavletich NP, Carver BS, Cordon-Cardo C, Erdjument-Bromage H, Tempst P, Chi SG, Kim HJ, Misteli T, Jiang X and Pandolfi PP. Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell. 2007; 128(1):141-156.
92. Geng F, Wenzel S and Tansey WP. Ubiquitin and proteasomes in transcription. Annual review of biochemistry. 2012; 81:177-201.
93. Salghetti SE, Kim SY and Tansey WP. Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc. The EMBO journal. 1999; 18(3):717-726.
94. Salghetti SE, Muratani M, Wijnen H, Futcher B and Tansey WP. Functional overlap of sequences that activate transcription and signal ubiquitin-mediated proteolysis. Proceedings of the National Academy of Sciences of the United States of America. 2000; 97(7):3118-3123.
95. Archer CT, Burdine L, Liu B, Ferdous A, Johnston SA and Kodadek T. Physical and functional interactions of monoubiquitylated transactivators with the proteasome. The Journal of biological chemistry. 2008; 283(31):21789-21798.
96. Bres V, Kiernan RE, Linares LK, Chable-Bessia C, Plechakova O, Treand C, Emiliani S, Peloponese JM, Jeang KT, Coux O, Scheffner M and Benkirane M. A non-proteolytic role for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter. Nature cell biology. 2003; 5(8):754-761.
97. Gammoh N, Gardiol D, Massimi P and Banks L. The Mdm2 ubiquitin ligase enhances transcriptional activity of human papillomavirus E2. Journal of virology. 2009; 83(3):1538-1543.
98. Greer SF, Zika E, Conti B, Zhu XS and Ting JP. Enhancement of CIITA transcriptional function by ubiquitin. Nature immunology. 2003; 4(11):1074-1082.
99. Brenkman AB, de Keizer PL, van den Broek NJ, Jochemsen AG and Burgering BM. Mdm2 induces mono-ubiquitination of FOXO4. PloS one. 2008; 3(7):e2819.
100. Thomas D and Tyers M. Transcriptional regulation: Kamikaze activators. Current biology: CB. 2000; 10(9):R341-343.
101. Salghetti SE, Caudy AA, Chenoweth JG and Tansey WP. Regulation of transcriptional activation domain function by ubiquitin. Science (New York, NY). 2001; 293(5535):1651-1653.
102. Molineaux SM. Molecular pathways: targeting proteasomal protein degradation in cancer. Clinical cancer research: an official journal of the American Association for Cancer Research. 2012; 18(1):15-20.
103. Kawabata S, Gills JJ, Mercado-Matos JR, Lopiccolo J, Wilson W, 3rd, Hollander MC and Dennis PA. Synergistic effects of nelfinavir and bortezomib on proteotoxic death of NSCLC and multiple myeloma cells. Cell death & disease. 2012; 3:e353.
104. Lichtenberg M, Mansilla A, Zecchini VR, Fleming A and Rubinsztein DC. The Parkinson's disease protein LRRK2 impairs proteasome substrate clearance without affecting proteasome catalytic activity. Cell death & disease. 2011; 2:e196.
105. Hideshima T, Richardson P, Chauhan D, Palombella VJ, Elliott PJ, Adams J and Anderson KC. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer research. 2001; 61(7):3071-3076.
106. Adams J. The development of proteasome inhibitors as anticancer drugs. Cancer cell. 2004; 5(5):417-421.
107. Fribley A, Zeng Q and Wang CY. Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells. Molecular and cellular biology. 2004; 24(22):9695-9704.
108. Hideshima T, Chauhan D, Richardson P, Mitsiades C, Mitsiades N, Hayashi T, Munshi N, Dang L, Castro A, Palombella V, Adams J and Anderson KC. NF-kappa B as a therapeutic target in multiple myeloma. The Journal of biological chemistry. 2002; 277(19):16639-16647.
109. Williams S, Pettaway C, Song R, Papandreou C, Logothetis C and McConkey DJ. Differential effects of the proteasome inhibitor bortezomib on apoptosis and angiogenesis in human prostate tumor xenografts. Molecular cancer therapeutics. 2003; 2(9):835-843.
110. Neri P, Ren L, Gratton K, Stebner E, Johnson J, Klimowicz A, Duggan P, Tassone P, Mansoor A, Stewart DA, Lonial S, Boise LH and Bahlis NJ. Bortezomib-induced "BRCAness" sensitizes multiple myeloma cells to PARP inhibitors. Blood. 2011; 118(24):6368-6379.
111. Nowis D, Maczewski M, Mackiewicz U, Kujawa M, Ratajska A, Wieckowski MR, Wilczynski GM, Malinowska M, Bil J, Salwa P, Bugajski M, Wojcik C, Sinski M, Abramczyk P, Winiarska M, Dabrowska-Iwanicka A, et al. Cardiotoxicity of the anticancer therapeutic agent bortezomib. The American journal of pathology. 2010; 176(6):2658-2668.
112. Oerlemans R, Franke NE, Assaraf YG, Cloos J, van Zantwijk I, Berkers CR, Scheffer GL, Debipersad K, Vojtekova K, Lemos C, van der Heijden JW, Ylstra B, Peters GJ, Kaspers GL, Dijkmans BA, Scheper RJ, et al. Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein. Blood. 2008; 112(6):2489-2499.
113. Suzuki E, Demo S, Deu E, Keats J, Arastu-Kapur S, Bergsagel PL, Bennett MK and Kirk CJ. Molecular mechanisms of bortezomib resistant adenocarcinoma cells. PloS one. 2011; 6(12):e27996.
114. Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA and Orlowski RZ. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007; 110(9):3281-3290.
115. Bhutani S, Das A, Maheshwari M, Lakhotia SC and Jana NR. Dysregulation of core components of SCF complex in poly-glutamine disorders. Cell death & disease. 2012; 3:e428.
116. Chatterjee A, Chatterjee U and Ghosh MK. Activation of protein kinase CK2 attenuates FOXO3a functioning in a PML-dependent manner: implications in human prostate cancer. Cell death & disease. 2013; 4:e543.
117. Costa AC, Loh SH and Martins LM. Drosophila Trap1 protects against mitochondrial dysfunction in a PINK1/parkin model of Parkinson's disease. Cell death & disease. 2013; 4:e467.
118. Gillissen B, Richter A, Richter A, Overkamp T, Essmann F, Hemmati PG, Preissner R, Belka C and Daniel PT. Targeted therapy of the XIAP/proteasome pathway overcomes TRAIL-resistance in carcinoma by switching apoptosis signaling to a Bax/Bak-independent 'type I' mode. Cell death & disease. 2013; 4:e643.
119. Kim AD, Kang KA, Kim HS, Kim DH, Choi YH, Lee SJ, Kim HS and Hyun JW. A ginseng metabolite, compound K, induces autophagy and apoptosis via generation of reactive oxygen species and activation of JNK in human colon cancer cells. Cell death & disease. 2013; 4:e750.
120. Pal P, Lochab S, Kanaujiya JK, Kapoor I, Sanyal S, Behre G and Trivedi AK. E6AP, an E3 ubiquitin ligase negatively regulates granulopoiesis by targeting transcription factor C/EBPalpha for ubiquitin-mediated proteasome degradation. Cell death & disease. 2013; 4:e590.
121. Santin I, Moore F, Grieco FA, Marchetti P, Brancolini C and Eizirik DL. USP18 is a key regulator of the interferon-driven gene network modulating pancreatic beta cell inflammation and apoptosis. Cell death & disease. 2012; 3:e419.
122. Wong VK, Li T, Law BY, Ma ED, Yip NC, Michelangeli F, Law CK, Zhang MM, Lam KY, Chan PL and Liu L. Saikosaponin-d, a novel SERCA inhibitor, induces autophagic cell death in apoptosis-defective cells. Cell death & disease. 2013; 4:e720.
123. da Silva SR, Paiva SL, Lukkarila JL and Gunning PT. Exploring a new frontier in cancer treatment: targeting the ubiquitin and ubiquitin-like activating enzymes. Journal of medicinal chemistry. 2013; 56(6):2165-2177.
124. Yang Y, Kitagaki J, Dai RM, Tsai YC, Lorick KL, Ludwig RL, Pierre SA, Jensen JP, Davydov IV, Oberoi P, Li CC, Kenten JH, Beutler JA, Vousden KH and Weissman AM. Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. Cancer research. 2007; 67(19):9472-9481.
125. Boggio R, Colombo R, Hay RT, Draetta GF and Chiocca S. A mechanism for inhibiting the SUMO pathway. Molecular cell. 2004; 16(4):549-561.
126. Fukuda I, Ito A, Hirai G, Nishimura S, Kawasaki H, Saitoh H, Kimura K, Sodeoka M and Yoshida M. Ginkgolic acid inhibits protein SUMOylation by blocking formation of the E1-SUMO intermediate. Chemistry & biology. 2009; 16(2):133-140.
127. Lu X, Olsen SK, Capili AD, Cisar JS, Lima CD and Tan DS. Designed semisynthetic protein inhibitors of Ub/Ubl E1 activating enzymes. Journal of the American Chemical Society. 2010; 132(6):1748-1749.
128. Soucy TA, Smith PG, Milhollen MA, Berger AJ, Gavin JM, Adhikari S, Brownell JE, Burke KE, Cardin DP, Critchley S, Cullis CA, Doucette A, Garnsey JJ, Gaulin JL, Gershman RE, Lublinsky AR, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009; 458(7239):732-736.
129. Yao WT, Wu JF, Yu GY, Wang R, Wang K, Li LH, Chen P, Jiang YN, Cheng H, Lee HW, Yu J, Qi H, Yu XJ, Wang P, Chu YW, Yang M, et al. Suppression of tumor angiogenesis by targeting the protein neddylation pathway. Cell death & disease. 2014; 5:e1059.
130. Milhollen MA, Traore T, Adams-Duffy J, Thomas MP, Berger AJ, Dang L, Dick LR, Garnsey JJ, Koenig E, Langston SP, Manfredi M, Narayanan U, Rolfe M, Staudt LM, Soucy TA, Yu J, et al. MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma. Blood. 2010; 116(9):1515-1523.
131. Ceccarelli DF, Tang X, Pelletier B, Orlicky S, Xie W, Plantevin V, Neculai D, Chou YC, Ogunjimi A, Al-Hakim A, Varelas X, Koszela J, Wasney GA, Vedadi M, Dhe-Paganon S, Cox S, et al. An allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme. Cell. 2011; 145(7):1075-1087.
132. Pulvino M, Liang Y, Oleksyn D, DeRan M, Van Pelt E, Shapiro J, Sanz I, Chen L and Zhao J. Inhibition of proliferation and survival of diffuse large B-cell lymphoma cells by a small-molecule inhibitor of the ubiquitin-conjugating enzyme Ubc13-Uev1A. Blood. 2012; 120(8):1668-1677.
133. Varshavsky A. The ubiquitin system, an immense realm. Annual review of biochemistry. 2012; 81:167-176.
134. Mattern MR, Wu J and Nicholson B. Ubiquitin-based anticancer therapy: carpet bombing with proteasome inhibitors vs surgical strikes with E1, E2, E3, or DUB inhibitors. Biochimica et biophysica acta. 2012; 1823(11):2014-2021.
135. de Bie P and Ciechanover A. Ubiquitination of E3 ligases: self-regulation of the ubiquitin system via proteolytic and non-proteolytic mechanisms. Cell death and differentiation. 2011; 18(9):1393-1402.
136. Fan YH, Cheng J, Vasudevan SA, Dou J, Zhang H, Patel RH, Ma IT, Rojas Y, Zhao Y, Yu Y, Zhang H, Shohet JM, Nuchtern JG, Kim ES and Yang J. USP7 inhibitor P22077 inhibits neuroblastoma growth via inducing p53-mediated apoptosis. Cell death & disease. 2013; 4:e867.
137. Mazza D, Infante P, Colicchia V, Greco A, Alfonsi R, Siler M, Antonucci L, Po A, De Smaele E, Ferretti E, Capalbo C, Bellavia D, Canettieri G, Giannini G, Screpanti I, Gulino A, et al. PCAF ubiquitin ligase activity inhibits Hedgehog/Gli1 signaling in p53-dependent response to genotoxic stress. Cell death and differentiation. 2013; 20(12):1688-1697.
138. Sermeus A and Michiels C. Reciprocal influence of the p53 and the hypoxic pathways. Cell death & disease. 2011; 2:e164.
139. Vousden KH and Prives C. Blinded by the Light: The Growing Complexity of p53. Cell. 2009; 137(3):413-431.
140. Chen YC, Chan JY, Chiu YL, Liu ST, Lozano G, Wang SL, Ho CL and Huang SM. Grail as a molecular determinant for the functions of the tumor suppressor p53 in tumorigenesis. Cell death and differentiation. 2013; 20(5):732-743.
141. Olivier M, Eeles R, Hollstein M, Khan MA, Harris CC and Hainaut P. The IARC TP53 database: new online mutation analysis and recommendations to users. Human mutation. 2002; 19(6):607-614.
142. Oliner JD, Kinzler KW, Meltzer PS, George DL and Vogelstein B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 1992; 358(6381):80-83.
143. Hoe KK, Verma CS and Lane DP. Drugging the p53 pathway: understanding the route to clinical efficacy. Nature reviews Drug discovery. 2014; 13(3):217-236.
144. Ray-Coquard I, Blay JY, Italiano A, Le Cesne A, Penel N, Zhi J, Heil F, Rueger R, Graves B, Ding M, Geho D, Middleton SA, Vassilev LT, Nichols GL and Bui BN. Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. The lancet oncology. 2012; 13(11):1133-1140.
145. Kracikova M, Akiri G, George A, Sachidanandam R and Aaronson SA. A threshold mechanism mediates p53 cell fate decision between growth arrest and apoptosis. Cell death and differentiation. 2013; 20(4):576-588.
146. Chillemi G, Davidovich P, D'Abramo M, Mametnabiev T, Garabadzhiu AV, Desideri A and Melino G. Molecular dynamics of the full-length p53 monomer. Cell cycle (Georgetown, Tex). 2013; 12(18):3098-3108.
147. Zambetti GP. Expanding the reach of the p53 tumor suppressor network. Cell death and differentiation. 2014; 21(4):505-506.
148. Martynova E, Pozzi S, Basile V, Dolfini D, Zambelli F, Imbriano C, Pavesi G and Mantovani R. Gain-of-function p53 mutants have widespread genomic locations partially overlapping with p63. Oncotarget. 2012; 3(2):132-143.
149. Kadakia MP, De-Fromentel CC and Sabapathy K. The 5th International p63/p73 workshop: much more than just tumour suppression. Cell death and differentiation. 2012; 19(3):549-550.
150. Amelio I, Grespi F, Annicchiarico-Petruzzelli M and Melino G. p63 the guardian of human reproduction. Cell cycle (Georgetown, Tex). 2012; 11(24):4545-4551.
151. Levine AJ, Tomasini R, McKeon FD, Mak TW and Melino G. The p53 family: guardians of maternal reproduction. Nat Rev Mol Cell Bio. 2011; 12(4):259.
152. Tomasini R, Mak TW and Melino G. The impact of p53 and p73 on aneuploidy and cancer. Trends in cell biology. 2008; 18(5):244-252.
153. Billon N, Terrinoni A, Jolicoeur C, McCarthy A, Richardson WD, Melino G and Raff M. Roles for p53 and p73 during oligodendrocyte development. Development. 2004; 131(6):1211-1220.
154. Masse I, Barbollat-Boutrand L, Molina M, Berthier-Vergnes O, Joly-Tonetti N, Martin MT, Caron de Fromentel C, Kanitakis J and Lamartine J. Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes. Cell death & disease. 2012; 3:e318.
155. Paris M, Rouleau M, Puceat M and Aberdam D. Regulation of skin aging and heart development by TAp63. Cell death and differentiation. 2012; 19(2):186-193.
156. Chari NS, Romano RA, Koster MI, Jaks V, Roop D, Flores ER, Teglund S, Sinha S, Gruber W, Aberger F, Medeiros LJ, Toftgard R and McDonnell TJ. Interaction between the TP63 and SHH pathways is an important determinant of epidermal homeostasis. Cell death and differentiation. 2013; 20(8):1080-1088.
157. Candi E, Rufini A, Terrinoni A, Giamboi-Miraglia A, Lena AM, Mantovani R, Knight R and Melino G. DeltaNp63 regulates thymic development through enhanced expression of FgfR2 and Jag2. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(29):11999-12004.
158. Tomasini R, Secq V, Pouyet L, Thakur AK, Wilhelm M, Nigri J, Vasseur S, Berthezene P, Calvo E, Melino G, Mak TW and Iovanna JL. TAp73 is required for macrophage-mediated innate immunity and the resolution of inflammatory responses. Cell death and differentiation. 2013; 20(2):293-301.
159. Yallowitz AR, Alexandrova EM, Talos F, Xu S, Marchenko ND and Moll UM. p63 is a prosurvival factor in the adult mammary gland during post-lactational involution, affecting PI-MECs and ErbB2 tumorigenesis. Cell death and differentiation. 2014; 21(4):645-654.
160. Burnley P, Rahman M, Wang H, Zhang Z, Sun X, Zhuge Q and Su DM. Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging. Cell death & disease. 2013; 4:e932.
161. Rufini A, Niklison-Chirou MV, Inoue S, Tomasini R, Harris IS, Marino A, Federici M, Dinsdale D, Knight RA, Melino G and Mak TW. TAp73 depletion accelerates aging through metabolic dysregulation. Gene Dev. 2012; 26(18):2009-2014.
162. Celardo I, Grespi F, Antonov A, Bernassola F, Garabadgiu AV, Melino G and Amelio I. Caspase-1 is a novel target of p63 in tumor suppression. Cell death & disease. 2013; 4:e645.
163. Manzl C, Fava LL, Krumschnabel G, Peintner L, Tanzer MC, Soratroi C, Bock FJ, Schuler F, Luef B, Geley S and Villunger A. Death of p53-defective cells triggered by forced mitotic entry in the presence of DNA damage is not uniquely dependent on Caspase-2 or the PIDDosome. Cell death & disease. 2013; 4:e942.
164. Melino G, Knight RA and Nicotera P. How many ways to die? How many different models of cell death? Cell death and differentiation. 2005; 12:1457-1462.
165. Evangelou K, Bartkova J, Kotsinas A, Pateras IS, Liontos M, Velimezi G, Kosar M, Liloglou T, Trougakos IP, Dyrskjot L, Andersen CL, Papaioannou M, Drosos Y, Papafotiou G, Hodny Z, Sosa-Pineda B, et al. The DNA damage checkpoint precedes activation of ARF in response to escalating oncogenic stress during tumorigenesis. Cell death and differentiation. 2013; 20(11):1485-1497.
166. Louwen F and Yuan JP. Battle of the eternal rivals: restoring functional p53 and inhibiting Polo-like kinase 1 as cancer therapy. Oncotarget. 2013; 4(7):958-971.
167. Shekhar MPV, Kato I, Nangia-Makker P and Tait L. Comedo-DCIS is a precursor lesion for basal-like breast carcinoma: identification of a novel p63/Her2/neu expressing subgroup. Oncotarget. 2013; 4(2):231-241.
168. Giacobbe A, Bongiorno-Borbone L, Bernassola F, Terrinoni A, Markert EK, Levine AJ, Feng Z, Agostini M, Zolla L, Agro AF, Notterman DA, Melino G and Peschiaroli A. p63 regulates glutaminase 2 expression. Cell cycle (Georgetown, Tex). 2013; 12(9):1395-1405.
169. Montero J, Dutta C, van Bodegom D, Weinstock D and Letai A. p53 regulates a non-apoptotic death induced by ROS. Cell death and differentiation. 2013; 20(11):1465-1474.
170. He Z, Liu H, Agostini M, Yousefi S, Perren A, Tschan MP, Mak TW, Melino G and Simon HU. p73 regulates autophagy and hepatocellular lipid metabolism through a transcriptional activation of the ATG5 gene. Cell death and differentiation. 2013; 20(10):1415-1424.
171. Huang YP, Guerrero-Preston R and Ratovitski EA. Phospho-Delta Np63 alpha-dependent regulation of autophagic signaling through transcription and micro-RNA modulation. Cell cycle (Georgetown, Tex). 2012; 11(6):1247-1259.
172. Selvarajah J, Nathawat K, Moumen A, Ashcroft M and Carroll VA. Chemotherapy-mediated p53-dependent DNA damage response in clear cell renal cell carcinoma: role of the mTORC1/2 and hypoxia-inducible factor pathways. Cell death & disease. 2013; 4.
173. Neise D, Sohn D, Stefanski A, Goto H, Inagaki M, Wesselborg S, Budach W, Stuhler K and Janicke RU. The p90 ribosomal S6 kinase (RSK) inhibitor BI-D1870 prevents gamma irradiation-induced apoptosis and mediates senescence via RSK-and p53-independent accumulation of p21WAF1/CIP1. Cell death & disease. 2013; 4:e859.
174. Huang YP, Jeong JS, Okamura J, Sook-Kim M, Zhu H, Guerrero-Preston R and Ratovitski EA. Global tumor protein p53/p63 interactome Making a case for cisplatin chemoresistance. Cell cycle (Georgetown, Tex). 2012; 11(12):2367-2379.
175. Huang YP, Kesselman D, Kizub D, Guerrero-Preston R and Ratovitski EA. Phospho-Delta Np63 alpha/microRNA feedback regulation in squamous carcinoma cells upon cisplatin exposure. Cell cycle (Georgetown, Tex). 2013; 12(4):684-697.
176. Mattiske S, Ho K, Noll JE, Neilsen PM, Callen DF and Suetani RJ. TAp63 regulates oncogenic miR-155 to mediate migration and tumour growth. Oncotarget. 2013; 4(11):1894-1903.
177. Tucci P, Agostini M, Grespi F, Markert EK, Terrinoni A, Vousden KH, Muller PA, Dotsch V, Kehrloesser S, Sayan BS, Giaccone G, Lowe SW, Takahashi N, Vandenabeele P, Knight RA, Levine AJ, et al. Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109(38):15312-15317.
178. Marcel V, Petit I, Murray-Zmijewski F, Goullet de Rugy T, Fernandes K, Meuray V, Diot A, Lane DP, Aberdam D and Bourdon JC. Diverse p63 and p73 isoforms regulate Delta133p53 expression through modulation of the internal TP53 promoter activity. Cell death and differentiation. 2012; 19(5):816-826.
179. Melino G. p63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53. Cell death and differentiation. 2011; 18(9):1487-1499.
180. Neilsen PM, Noll JE, Suetani RJ, Schulz RB, Al-Ejeh F, Evdokiou A, Lane DP and Callen DF. Mutant p53 uses p63 as a molecular chaperone to alter gene expression and induce a pro-invasive secretome. Oncotarget. 2011; 2(12):1203-1217.
181. Luh LM, Kehrloesser S, Deutsch GB, Gebel J, Coutandin D, Schafer B, Agostini M, Melino G and Dotsch V. Analysis of the oligomeric state and transactivation potential of TAp73alpha. Cell death and differentiation. 2013; 20(8):1008-1016.
182. Yu Y, Huang H, Li J, Zhang J, Gao J, Lu B and Huang C. GADD45 beta mediates p53 protein degradation via Src/PP2A/MDM2 pathway upon arsenite treatment. Cell death & disease. 2013; 4.
183. Melino S, Bellomaria A, Nepravishta R, Paci R and Melino G. p63 threonine phosphorylation signals the interaction with the WW domain of the E3 ligase Itch. Cell cycle (Georgetown, Tex). 2014; in press.
184. Strano S, Munarriz E, Rossi M, Castagnoli L, Shaul Y, Sacchi A, Oren M, Sudol M, Cesareni G and Blandino G. Physical interaction with Yes-associated protein enhances p73 transcriptional activity. Journal of Biological Chemistry. 2001; 276(18):15164-15173.
185. Levy D, Adamovich Y, Reuven N and Shaul Y. The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73. Cell death and differentiation. 2007; 14(4):743-751.
186. Danovi SA, Rossi M, Gudmundsdottir K, Yuan M, Melino G and Basu S. Yes-Associated Protein (YAP) is a critical mediator of c-Jun-dependent apoptosis. Cell death and differentiation. 2008; 15(1):217-219.
187. Adamovich Y, Adler J, Meltser V, Reuven N and Shaul Y. AMPK couples p73 with p53 in cell fate decision. Cell death and differentiation. 2014.
188. Oberoi-Khanuja TK, Murali A and Rajalingam K. IAPs on the move: role of inhibitors of apoptosis proteins in cell migration. Cell death & disease. 2013; 4.
189. Tenev T, Ditzel M, Zachariou A and Meier P. The antiapoptotic activity of insect IAPs requires activation by an evolutionarily conserved mechanism. Cell death and differentiation. 2007; 14(6):1191-1201.
190. Yang WS, Cooke M, Duckett CS, Yang XL and Dorsey JF. Distinctive effects of the cellular inhibitor of apoptosis protein c-IAP2 through stabilization by XIAP in glioblastoma multiforme cells. Cell cycle (Georgetown, Tex). 2014; 13(6):992-1005.
191. Dubrez L, Berthelet J and Glorian V. IAP proteins as targets for drug development in oncology. OncoTargets and therapy. 2013; 9:1285-1304.
192. Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, Gillard JW, Jaquith JB, Morris SJ and Barker PA. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Molecular cell. 2008; 30(6):689-700.
193. Festjens N, Vanden Berghe T, Cornelis S and Vandenabeele P. RIP1, a kinase on the crossroads of a cell's decision to live or die. Cell death and differentiation. 2007; 14(3):400-410.
194. Wu H, Tschopp J and Lin SC. Smac mimetics and TNFalpha: a dangerous liaison? Cell. 2007; 131(4):655-658.
195. Tseng PH, Matsuzawa A, Zhang W, Mino T, Vignali DA and Karin M. Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines. Nature immunology. 2010; 11(1):70-75.
196. Wang G, Chan CH, Gao Y and Lin HK. Novel roles of Skp2 E3 ligase in cellular senescence, cancer progression, and metastasis. Chinese journal of cancer. 2012; 31(4):169-177.
197. Bloom J and Pagano M. Deregulated degradation of the cdk inhibitor p27 and malignant transformation. Seminars in cancer biology. 2003; 13(1):41-47.
198. Carrano AC, Eytan E, Hershko A and Pagano M. SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nature cell biology. 1999; 1(4):193-199.
199. Gstaiger M, Jordan R, Lim M, Catzavelos C, Mestan J, Slingerland J and Krek W. Skp2 is oncogenic and overexpressed in human cancers. Proceedings of the National Academy of Sciences of the United States of America. 2001; 98(9):5043-5048.
200. Tan P, Cady B, Wanner M, Worland P, Cukor B, Magi-Galluzzi C, Lavin P, Draetta G, Pagano M and Loda M. The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas. Cancer research. 1997; 57(7):1259-1263.
201. Chan CH, Morrow JK, Li CF, Gao Y, Jin G, Moten A, Stagg LJ, Ladbury JE, Cai Z, Xu D, Logothetis CJ, Hung MC, Zhang S and Lin HK. Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression. Cell. 2013; 154(3):556-568.
202. Ungermannova D, Lee J, Zhang G, Dallmann HG, McHenry CS and Liu X. High-throughput screening AlphaScreen assay for identification of small-molecule inhibitors of ubiquitin E3 ligase SCFSkp2-Cks1. Journal of biomolecular screening. 2013; 18(8):910-920.
203. Wu TY, Wagner KW, Bursulaya B, Schultz PG and Deveraux QL. Development and characterization of nonpeptidic small molecule inhibitors of the XIAP/caspase-3 interaction. Chemistry & biology. 2003; 10(8):759-767.
204. Aghajan M, Jonai N, Flick K, Fu F, Luo M, Cai X, Ouni I, Pierce N, Tang X, Lomenick B, Damoiseaux R, Hao R, Del Moral PM, Verma R, Li Y, Li C, et al. Chemical genetics screen for enhancers of rapamycin identifies a specific inhibitor of an SCF family E3 ubiquitin ligase. Nature biotechnology. 2010; 28(7):738-742.
205. Orlicky S, Tang X, Neduva V, Elowe N, Brown ED, Sicheri F and Tyers M. An allosteric inhibitor of substrate recognition by the SCF(Cdc4) ubiquitin ligase. Nature biotechnology. 2010; 28(7):733-737.
206. Reyes-Turcu FE, Ventii KH and Wilkinson KD. Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annual review of biochemistry. 2009; 78:363-397.
207. Ernst A, Avvakumov G, Tong J, Fan Y, Zhao Y, Alberts P, Persaud A, Walker JR, Neculai AM, Neculai D, Vorobyov A, Garg P, Beatty L, Chan PK, Juang YC, Landry MC, et al. A strategy for modulation of enzymes in the ubiquitin system. Science (New York, NY). 2013; 339(6119):590-595.
208. Zhang S and Du-Cuny L. Development and evaluation of a new statistical model for structure-based high-throughput virtual screening. International journal of bioinformatics research and applications. 2009; 5(3):269-279.
209. Lavecchia A, Di Giovanni C, Cerchia C, Russo A, Russo G and Novellino E. Discovery of a novel small molecule inhibitor targeting the frataxin/ubiquitin interaction via structure-based virtual screening and bioassays. Journal of medicinal chemistry. 2013; 56(7):2861-2873.
210. Higueruelo AP, Jubb H and Blundell TL. Protein-protein interactions as druggable targets: recent technological advances. Current opinion in pharmacology. 2013; 13(5):791-796.
211. Blackwell HE and Grubbs RH. Highly Efficient Synthesis of Covalently Cross-Linked Peptide Helices by Ring-Closing Metathesis. Angew Chem Int Ed. 1989; 37(23):3284.
212. Bernal F, Wade M, Godes M, Davis TN, Whitehead DG, Kung AL, Wahl GM and Walensky LD. A stapled p53 helix overcomes HDMX-mediated suppression of p53. Cancer cell. 2010; 18(5):411-422.
213. Brown CJ, Quah ST, Jong J, Goh AM, Chiam PC, Khoo KH, Choong ML, Lee MA, Yurlova L, Zolghadr K, Joseph TL, Verma CS and Lane DP. Stapled peptides with improved potency and specificity that activate p53. ACS chemical biology. 2013; 8(3):506-512.
214. Chang YS, Graves B, Guerlavais V, Tovar C, Packman K, To KH, Olson KA, Kesavan K, Gangurde P, Mukherjee A, Baker T, Darlak K, Elkin C, Filipovic Z, Qureshi FZ, Cai H, et al. Stapled alpha-helical peptide drug development: a potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy. Proceedings of the National Academy of Sciences of the United States of America. 2013; 110(36):E3445-3454.
215. Buckley DL, Gustafson JL, Van Molle I, Roth AG, Tae HS, Gareiss PC, Jorgensen WL, Ciulli A and Crews CM. Small-molecule inhibitors of the interaction between the E3 ligase VHL and HIF1alpha. Angewandte Chemie (International ed in English). 2012; 51(46):11463-11467.
216. Buckley DL, Van Molle I, Gareiss PC, Tae HS, Michel J, Noblin DJ, Jorgensen WL, Ciulli A and Crews CM. Targeting the von Hippel-Lindau E3 ubiquitin ligase using small molecules to disrupt the VHL/HIF-1alpha interaction. Journal of the American Chemical Society. 2012; 134(10):4465-4468.
217. Boisclair MD, McClure C, Josiah S, Glass S, Bottomley S, Kamerkar S and Hemmila I. Development of a ubiquitin transfer assay for high throughput screening by fluorescence resonance energy transfer. Journal of biomolecular screening. 2000; 5(5):319-328.
218. Davydov IV, Woods D, Safiran YJ, Oberoi P, Fearnhead HO, Fang S, Jensen JP, Weissman AM, Kenten JH and Vousden KH. Assay for ubiquitin ligase activity: high-throughput screen for inhibitors of HDM2. Journal of biomolecular screening. 2004; 9(8):695-703.
219. Huang J, Sheung J, Dong G, Coquilla C, Daniel-Issakani S and Payan DG. High-throughput screening for inhibitors of the e3 ubiquitin ligase APC. Methods in enzymology. 2005; 399:740-754.
220. Kus B, Gajadhar A, Stanger K, Cho R, Sun W, Rouleau N, Lee T, Chan D, Wolting C, Edwards A, Bosse R and Rotin D. A high throughput screen to identify substrates for the ubiquitin ligase Rsp5. The Journal of biological chemistry. 2005; 280(33):29470-29478.
221. Herman AG, Hayano M, Poyurovsky MV, Shimada K, Skouta R, Prives C and Stockwell BR. Discovery of Mdm2-MdmX E3 ligase inhibitors using a cell-based ubiquitination assay. Cancer discovery. 2011; 1(4):312-325.
222. Scheffner M and Kumar S. Mammalian HECT ubiquitin-protein ligases: biological and pathophysiological aspects. Biochimica et biophysica acta. 2014; 1843(1):61-74.
223. Rotblat B, Southwell AL, Ehrnhoefer DE, Skotte NH, Metzler M, Franciosi S, Leprivier G, Somasekharan SP, Barokas A, Deng Y, Tang T, Mathers J, Cetinbas N, Daugaard M, Kwok B, Li L, et al. HACE1 reduces oxidative stress and mutant Huntingtin toxicity by promoting the NRF2 response. Proceedings of the National Academy of Sciences of the United States of America. 2014; 111(8):3032-3037.
224. Rotin D and Kumar S. Physiological functions of the HECT family of ubiquitin ligases. Nature reviews Molecular cell biology. 2009; 10(6):398-409.
225. Marin I. Animal HECT ubiquitin ligases: evolution and functional implications. BMC evolutionary biology. 2010; 10:56.
226. Salah Z, Cohen S, Itzhaki E and Aqeilan RI. NEDD4 E3 ligase inhibits the activity of the Hippo pathway by targeting LATS1 for degradation. Cell cycle (Georgetown, Tex). 2013; 12(24):3817-3823.
227. Salah Z, Melino G and Aqeilan RI. Negative regulation of the Hippo pathway by E3 ubiquitin ligase ITCH is sufficient to promote tumorigenicity. Cancer research. 2011; 71(5):2010-2020.
228. Layfield R, Lowe J and Bedford L. The ubiquitin-proteasome system and neurodegenerative disorders. Essays in biochemistry. 2005; 41:157-171.
229. Rubinsztein DC. The roles of intracellular protein-degradation pathways in neurodegeneration. Nature. 2006; 443(7113):780-786.
230. Rossi M, Rotblat B, Ansell K, Amelio I, Caraglia M, Misso G, Bernassola F, Cavasotto CN, Knight RA, Ciechanover A and Melino G. High throughput screening for inhibitors of the HECT ubiquitin E3 ligase ITCH identifies antidepressant drugs as regulators of autophagy. Cell death & disease. 2014; 5:e1203.
231. Suryaraja R, Anitha M, Anbarasu K, Kumari G and Mahalingam S. The E3 ubiquitin ligase Itch regulates tumor suppressor protein RASSF5/NORE1 stability in an acetylation-dependent manner. Cell death & disease. 2013; 4.
232. Yamagishi Y, Shoji I, Miyagawa S, Kawakami T, Katoh T, Goto Y and Suga H. Natural product-like macrocyclic N-methyl-peptide inhibitors against a ubiquitin ligase uncovered from a ribosome-expressed de novo library. Chemistry & biology. 2011; 18(12):1562-1570.
233. Yang D, Li L, Liu H, Wu L, Luo Z, Li H, Zheng S, Gao H, Chu Y, Sun Y, Liu J and Jia L. Induction of autophagy and senescence by knockdown of ROC1 E3 ubiquitin ligase to suppress the growth of liver cancer cells. Cell death and differentiation. 2013; 20(2):235-247.
234. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N and Liu EA. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science (New York, NY). 2004; 303(5659):844-848.
235. Ding K, Lu Y, Nikolovska-Coleska Z, Wang G, Qiu S, Shangary S, Gao W, Qin D, Stuckey J, Krajewski K, Roller PP and Wang S. Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. Journal of medicinal chemistry. 2006; 49(12):3432-3435.
236. Shangary S, Qin D, McEachern D, Liu M, Miller RS, Qiu S, Nikolovska-Coleska Z, Ding K, Wang G, Chen J, Bernard D, Zhang J, Lu Y, Gu Q, Shah RB, Pienta KJ, et al. Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105(10):3933-3938.
237. Yang Y, Ludwig RL, Jensen JP, Pierre SA, Medaglia MV, Davydov IV, Safiran YJ, Oberoi P, Kenten JH, Phillips AC, Weissman AM and Vousden KH. Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer cell. 2005; 7(6):547-559.
238. Grasberger BL, Lu T, Schubert C, Parks DJ, Carver TE, Koblish HK, Cummings MD, LaFrance LV, Milkiewicz KL, Calvo RR, Maguire D, Lattanze J, Franks CF, Zhao S, Ramachandren K, Bylebyl GR, et al. Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells. Journal of medicinal chemistry. 2005; 48(4):909-912.
239. Cai Q, Sun H, Peng Y, Lu J, Nikolovska-Coleska Z, McEachern D, Liu L, Qiu S, Yang CY, Miller R, Yi H, Zhang T, Sun D, Kang S, Guo M, Leopold L, et al. A potent and orally active antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in clinical development for cancer treatment. Journal of medicinal chemistry. 2011; 54(8):2714-2726.
240. Flygare JA, Beresini M, Budha N, Chan H, Chan IT, Cheeti S, Cohen F, Deshayes K, Doerner K, Eckhardt SG, Elliott LO, Feng B, Franklin MC, Reisner SF, Gazzard L, Halladay J, et al. Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). Journal of medicinal chemistry. 2012; 55(9):4101-4113.
241. Cao XR, Lill NL, Boase N, Shi PP, Croucher DR, Shan H, Qu J, Sweezer EM, Place T, Kirby PA, Daly RJ, Kumar S and Yang B. Nedd4 controls animal growth by regulating IGF-1 signaling. Science signaling. 2008; 1(38):ra5.
242. Nagpal P, Plant PJ, Correa J, Bain A, Takeda M, Kawabe H, Rotin D, Bain JR and Batt JA. The ubiquitin ligase Nedd4-1 participates in denervation-induced skeletal muscle atrophy in mice. PloS one. 2012; 7(10):e46427.
243. Liu PY, Xu N, Malyukova A, Scarlett CJ, Sun YT, Zhang XD, Ling D, Su SP, Nelson C, Chang DK, Koach J, Tee AE, Haber M, Norris MD, Toon C, Rooman I, et al. The histone deacetylase SIRT2 stabilizes Myc oncoproteins. Cell death and differentiation. 2013; 20(3):503-514.
244. Yasuda J, Nakao M, Kawaoka Y and Shida H. Nedd4 regulates egress of Ebola virus-like particles from host cells. Journal of virology. 2003; 77(18):9987-9992.
245. Timmins J, Schoehn G, Ricard-Blum S, Scianimanico S, Vernet T, Ruigrok RW and Weissenhorn W. Ebola virus matrix protein VP40 interaction with human cellular factors Tsg101 and Nedd4. Journal of molecular biology. 2003; 326(2):493-502.
246. Blot V, Perugi F, Gay B, Prevost MC, Briant L, Tangy F, Abriel H, Staub O, Dokhelar MC and Pique C. Nedd4.1-mediated ubiquitination and subsequent recruitment of Tsg101 ensure HTLV-1 Gag trafficking towards the multivesicular body pathway prior to virus budding. Journal of cell science. 2004; 117(Pt 11):2357-2367.
247. Kikonyogo A, Bouamr F, Vana ML, Xiang Y, Aiyar A, Carter C and Leis J. Proteins related to the Nedd4 family of ubiquitin protein ligases interact with the L domain of Rous sarcoma virus and are required for gag budding from cells. Proceedings of the National Academy of Sciences of the United States of America. 2001; 98(20):11199-11204.
248. Yasuda J, Hunter E, Nakao M and Shida H. Functional involvement of a novel Nedd4-like ubiquitin ligase on retrovirus budding. EMBO reports. 2002; 3(7):636-640.
249. Bouamr F, Melillo JA, Wang MQ, Nagashima K, de Los Santos M, Rein A and Goff SP. PPPYVEPTAP motif is the late domain of human T-cell leukemia virus type 1 Gag and mediates its functional interaction with cellular proteins Nedd4 and Tsg101 [corrected]. Journal of virology. 2003; 77(22):11882-11895.
250. Vana ML, Tang Y, Chen A, Medina G, Carter C and Leis J. Role of Nedd4 and ubiquitination of Rous sarcoma virus Gag in budding of virus-like particles from cells. Journal of virology. 2004; 78(24):13943-13953.
251. Perry WL, Hustad CM, Swing DA, O'Sullivan TN, Jenkins NA and Copeland NG. The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice. Nature genetics. 1998; 18(2):143-146.
252. Lifton RP. Genetic determinants of human hypertension. Proceedings of the National Academy of Sciences of the United States of America. 1995; 92(19):8545-8551.
253. Shi PP, Cao XR, Sweezer EM, Kinney TS, Williams NR, Husted RF, Nair R, Weiss RM, Williamson RA, Sigmund CD, Snyder PM, Staub O, Stokes JB and Yang B. Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4-2. American journal of physiology Renal physiology. 2008; 295(2):F462-470.
254. Zhi X and Chen C. WWP1: a versatile ubiquitin E3 ligase in signaling and diseases. Cellular and molecular life sciences: CMLS. 2012; 69(9):1425-1434.
255. Rivetti di Val Cervo P, Tucci P, Majid A, Lena AM, Agostini M, Bernardini S, Candi E, Cohen G, Nicotera P, Dyer MJ and Melino G. p73, miR106b, miR34a, and Itch in chronic lymphocytic leukemia. Blood. 2009; 113(25):6498-6499; author reply 6499-6500.
256. Zhang L, Haraguchi S, Koda T, Hashimoto K and Nakagawara A. Muscle atrophy and motor neuron degeneration in human NEDL1 transgenic mice. Journal of biomedicine & biotechnology. 2011; 2011:831092.
257. Li Y, Ozaki T, Kikuchi H, Yamamoto H, Ohira M and Nakagawara A. A novel HECT-type E3 ubiquitin protein ligase NEDL1 enhances the p53-mediated apoptotic cell death in its catalytic activity-independent manner. Oncogene. 2008; 27(26):3700-3709.
258. Shinada K, Tsukiyama T, Sho T, Okumura F, Asaka M and Hatakeyama S. RNF43 interacts with NEDL1 and regulates p53-mediated transcription. Biochem Biophys Res Commun. 2011; 404(1):143-147.
259. Zou W, Chen X, Shim JH, Huang Z, Brady N, Hu D, Drapp R, Sigrist K, Glimcher LH and Jones D. The E3 ubiquitin ligase Wwp2 regulates craniofacial development through mono-ubiquitylation of Goosecoid. Nature cell biology. 2011; 13(1):59-65.
260. Chong-Kopera H, Inoki K, Li Y, Zhu T, Garcia-Gonzalo FR, Rosa JL and Guan KL. TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase. The Journal of biological chemistry. 2006; 281(13):8313-8316.
261. Diouf B, Cheng Q, Krynetskaia NF, Yang W, Cheok M, Pei D, Fan Y, Cheng C, Krynetskiy EY, Geng H, Chen S, Thierfelder WE, Mullighan CG, Downing JR, Hsieh P, Pui CH, et al. Somatic deletions of genes regulating MSH2 protein stability cause DNA mismatch repair deficiency and drug resistance in human leukemia cells. Nature medicine. 2011; 17(10):1298-1303.
262. Miyazaki K, Fujita T, Ozaki T, Kato C, Kurose Y, Sakamoto M, Kato S, Goto T, Itoyama Y, Aoki M and Nakagawara A. NEDL1, a novel ubiquitin-protein isopeptide ligase for dishevelled-1, targets mutant superoxide dismutase-1. The Journal of biological chemistry. 2004; 279(12):11327-11335.
263. Bekker-Jensen S, Rendtlew Danielsen J, Fugger K, Gromova I, Nerstedt A, Lukas C, Bartek J, Lukas J and Mailand N. HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Nature cell biology. 2010; 12(1):80-86; sup pp 81-12.
264. Danielsen JR, Povlsen LK, Villumsen BH, Streicher W, Nilsson J, Wikstrom M, Bekker-Jensen S and Mailand N. DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding Zinc finger. The Journal of cell biology. 2012; 197(2):179-187.
265. Puffenberger EG, Jinks RN, Wang H, Xin B, Fiorentini C, Sherman EA, Degrazio D, Shaw C, Sougnez C, Cibulskis K, Gabriel S, Kelley RI, Morton DH and Strauss KA. A homozygous missense mutation in HERC2 associated with global developmental delay and autism spectrum disorder. Human mutation. 2012; 33(12):1639-1646.
266. Harlalka GV, Baple EL, Cross H, Kuhnle S, Cubillos-Rojas M, Matentzoglu K, Patton MA, Wagner K, Coblentz R, Ford DL, Mackay DJ, Chioza BA, Scheffner M, Rosa JL and Crosby AH. Mutation of HERC2 causes developmental delay with Angelman-like features. Journal of medical genetics. 2013; 50(2):65-73.
267. Kishino T, Lalande M and Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nature genetics. 1997; 15(1):70-73.
268. Matsuura T, Sutcliffe JS, Fang P, Galjaard RJ, Jiang YH, Benton CS, Rommens JM and Beaudet AL. De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nature genetics. 1997; 15(1):74-77.
269. Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S, Zhang H, Estes A, Brune CW, Bradfield JP, Imielinski M, Frackelton EC, Reichert J, Crawford EL, Munson J, Sleiman PM, et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature. 2009; 459(7246):569-573.
270. Hogart A, Wu D, LaSalle JM and Schanen NC. The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13. Neurobiology of disease. 2010; 38(2):181-191.
271. Durfee LA, Lyon N, Seo K and Huibregtse JM. The ISG15 conjugation system broadly targets newly synthesized proteins: implications for the antiviral function of ISG15. Molecular cell. 2010; 38(5):722-732.
272. Zhao C, Hsiang TY, Kuo RL and Krug RM. ISG15 conjugation system targets the viral NS1 protein in influenza A virus-infected cells. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107(5):2253-2258.
273. Adhikary S, Marinoni F, Hock A, Hulleman E, Popov N, Beier R, Bernard S, Quarto M, Capra M, Goettig S, Kogel U, Scheffner M, Helin K and Eilers M. The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation. Cell. 2005; 123(3):409-421.
274. Chen D, Brooks CL and Gu W. ARF-BP1 as a potential therapeutic target. British journal of cancer. 2006; 94(11):1555-1558.
275. Confalonieri S, Quarto M, Goisis G, Nuciforo P, Donzelli M, Jodice G, Pelosi G, Viale G, Pece S and Di Fiore PP. Alterations of ubiquitin ligases in human cancer and their association with the natural history of the tumor. Oncogene. 2009; 28(33):2959-2968.
276. Beaudenon S and Huibregtse JM. HPV E6, E6AP and cervical cancer. BMC biochemistry. 2008; 9 Suppl 1:S4.
277. Clancy JL, Henderson MJ, Russell AJ, Anderson DW, Bova RJ, Campbell IG, Choong DY, Macdonald GA, Mann GJ, Nolan T, Brady G, Olopade OI, Woollatt E, Davies MJ, Segara D, Hacker NF, et al. EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer. Oncogene. 2003; 22(32):5070-5081.
278. Fuja TJ, Lin F, Osann KE and Bryant PJ. Somatic mutations and altered expression of the candidate tumor suppressors CSNK1 epsilon, DLG1, and EDD/hHYD in mammary ductal carcinoma. Cancer research. 2004; 64(3):942-951.
279. Chen D, Yoon JB and Gu W. Reactivating the ARF-p53 axis in AML cells by targeting ULF. Cell cycle (Georgetown, Tex). 2010; 9(15):2946-2951.
280. Zhang L, Anglesio MS, O'Sullivan M, Zhang F, Yang G, Sarao R, Mai PN, Cronin S, Hara H, Melnyk N, Li L, Wada T, Liu PP, Farrar J, Arceci RJ, Sorensen PH, et al. The E3 ligase HACE1 is a critical chromosome 6q21 tumor suppressor involved in multiple cancers. Nature medicine. 2007; 13(9):1060-1069.
281. Slade I, Stephens P, Douglas J, Barker K, Stebbings L, Abbaszadeh F, Pritchard-Jones K, Cole R, Pizer B, Stiller C, Vujanic G, Scott RH, Stratton MR and Rahman N. Constitutional translocation breakpoint mapping by genome-wide paired-end sequencing identifies HACE1 as a putative Wilms tumour susceptibility gene. Journal of medical genetics. 2010; 47(5):342-347