Gene Symbol: UBC
Description: ubiquitin C
Alias: HMG20, polyubiquitin-C
Species: human
Products:     UBC

Top Publications

  1. Liu Y, Soetandyo N, Lee J, Liu L, Xu Y, Clemons W, et al. USP13 antagonizes gp78 to maintain functionality of a chaperone in ER-associated degradation. elife. 2014;3:e01369 pubmed publisher
    ..DOI: http://dx.doi.org/10.7554/eLife.01369.001. ..
  2. Kane L, Lazarou M, Fogel A, Li Y, Yamano K, Sarraf S, et al. PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol. 2014;205:143-53 pubmed publisher
    ..These results explain a feed-forward mechanism of PINK1-mediated initiation of Parkin E3 ligase activity. ..
  3. Liu W, Shang Y, Zeng Y, Liu C, Li Y, Zhai L, et al. Dimeric Ube2g2 simultaneously engages donor and acceptor ubiquitins to form Lys48-linked ubiquitin chains. EMBO J. 2014;33:46-61 pubmed publisher
    ..These results reveal an unanticipated mode of E2 self-association that allows the E2 to effectively engage two ubiquitins to specifically synthesize Lys48-linked ubiquitin chains. ..
  4. Fujita H, Rahighi S, Akita M, Kato R, Sasaki Y, Wakatsuki S, et al. Mechanism underlying I?B kinase activation mediated by the linear ubiquitin chain assembly complex. Mol Cell Biol. 2014;34:1322-35 pubmed publisher
  5. Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, et al. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature. 2014;510:162-6 pubmed publisher
    ..Our results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity. These findings demonstrate that phosphorylated ubiquitin is a parkin activator...
  6. Huang Y, Leung J, Lowery M, Matsushita N, Wang Y, Shen X, et al. Modularized functions of the Fanconi anemia core complex. Cell Rep. 2014;7:1849-57 pubmed publisher
    ..Our work reveals the roles of several FA gene products with previously undefined functions and a modularized assembly of the FA core complex. ..
  7. Rizzo A, Salerno P, Bezsonova I, Korzhnev D. NMR structure of the human Rad18 zinc finger in complex with ubiquitin defines a class of UBZ domains in proteins linked to the DNA damage response. Biochemistry. 2014;53:5895-906 pubmed publisher
  8. Roff M, Thompson J, Rodriguez M, Jacque J, Baleux F, Arenzana Seisdedos F, et al. Role of IkappaBalpha ubiquitination in signal-induced activation of NFkappaB in vivo. J Biol Chem. 1996;271:7844-50 pubmed
    ..Thus signal-induced activation of NF-kappaB involves phosphorylation-dependent ubiquitination of IkappaBalpha, which targets the protein for rapid degradation by the proteasome and releases NF-kappaB for translocation to the nucleus. ..
  9. Kumar S, Kao W, Howley P. Physical interaction between specific E2 and Hect E3 enzymes determines functional cooperativity. J Biol Chem. 1997;272:13548-54 pubmed

More Information

Publications403 found, 100 shown here

  1. Wilkinson C, Seeger M, Hartmann Petersen R, Stone M, Wallace M, Semple C, et al. Proteins containing the UBA domain are able to bind to multi-ubiquitin chains. Nat Cell Biol. 2001;3:939-43 pubmed
    ..These two proteins are implicated, along with the fission-yeast Pus1(S5a/Rpn10) subunit of the 26 S proteasome, in the recognition and turnover of substrates by this proteolytic complex. ..
  2. Ogawara Y, Kishishita S, Obata T, Isazawa Y, Suzuki T, Tanaka K, et al. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J Biol Chem. 2002;277:21843-50 pubmed
    ..This study may shed light on the mechanisms by which Akt promotes survival, proliferation, and tumorigenesis. ..
  3. Jiang Z, Zamanian Daryoush M, Nie H, Silva A, Williams B, Li X. Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFkappa B and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3-TRAF6-TAK1-TAB2-PKR . J Biol Chem. 2003;278:16713-9 pubmed
    ..Kinase inactive mutants of TAK1 (TAK1DN) and PKR (PKRDN) inhibit poly(dI.dC)-induced TLR3-mediated NFkappaB activation, suggesting that both of these kinases play important roles in this pathway. ..
  4. Miyazaki K, Ozaki T, Kato C, Hanamoto T, Fujita T, Irino S, et al. A novel HECT-type E3 ubiquitin ligase, NEDL2, stabilizes p73 and enhances its transcriptional activity. Biochem Biophys Res Commun. 2003;308:106-13 pubmed
    ..Consistent with the NEDL2-mediated stabilization of p73, NEDL2 enhanced the p73-dependent transcriptional activation. Thus, our results suggest that NEDL2 activates the function of p73 by increasing its stability. ..
  5. Kang Y, Vossler R, Diaz Martinez L, Winter N, Clarke D, Walters K. UBL/UBA ubiquitin receptor proteins bind a common tetraubiquitin chain. J Mol Biol. 2006;356:1027-35 pubmed
    ..Altogether our results suggest a mechanism through which UBL/UBA proteins could protect chains from premature de-ubiquitylation and unnecessary elongation during their transit to the proteasome. ..
  6. Cavey J, Ralston S, Sheppard P, Ciani B, Gallagher T, Long J, et al. Loss of ubiquitin binding is a unifying mechanism by which mutations of SQSTM1 cause Paget's disease of bone. Calcif Tissue Int. 2006;78:271-7 pubmed
  7. Tang J, Qu L, Zhang J, Wang W, Michaelson J, Degenhardt Y, et al. Critical role for Daxx in regulating Mdm2. Nat Cell Biol. 2006;8:855-62 pubmed
    ..These findings reveal that Daxx modulates the function of Mdm2 at multiple levels and suggest that the disruption of the Mdm2-Daxx interaction may be important for p53 activation in response to DNA damage. ..
  8. Scaglioni P, Yung T, Cai L, Erdjument Bromage H, Kaufman A, Singh B, et al. A CK2-dependent mechanism for degradation of the PML tumor suppressor. Cell. 2006;126:269-83 pubmed
    ..These data identify a key posttranslational mechanism that controls PML protein levels and provide therapeutic means toward PML restoration through CK2 inhibition. ..
  9. Lee J, Song B, DeBose Boyd R, Ye J. Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin ligase gp78. J Biol Chem. 2006;281:39308-15 pubmed
  10. Esapa C, Waite A, Locke M, Benson M, Kraus M, McIlhinney R, et al. SGCE missense mutations that cause myoclonus-dystonia syndrome impair epsilon-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA. Hum Mol Genet. 2007;16:327-42 pubmed
  11. Hövelmeyer N, Wunderlich F, Massoumi R, Jakobsen C, Song J, Wörns M, et al. Regulation of B cell homeostasis and activation by the tumor suppressor gene CYLD. J Exp Med. 2007;204:2615-27 pubmed
    ..These findings suggest that CYLD can both positively and negatively regulate signal transduction and homeostasis of B cells in vivo, depending on the expression of CYLD splice variants. ..
  12. Shen Y, Hirsch D, SASIELA C, Wu W. Cdc42 regulates E-cadherin ubiquitination and degradation through an epidermal growth factor receptor to Src-mediated pathway. J Biol Chem. 2008;283:5127-37 pubmed
    ..Our data support a model that activation of Cdc42 contributes to mesenchyme-like phenotype by targeting of E-cadherin for lysosomal degradation. ..
  13. Ikeda H, Kerppola T. Lysosomal localization of ubiquitinated Jun requires multiple determinants in a lysine-27-linked polyubiquitin conjugate. Mol Biol Cell. 2008;19:4588-601 pubmed publisher
    ..Lysosomal localization of the conjugate requires determinants in Jun and in ubiquitin that are recognized in part by TSG101 and HRS, facilitating selective translocation and degradation of ubiquitinated Jun. ..
  14. Edelmann M, Iphöfer A, Akutsu M, Altun M, Di Gleria K, Kramer H, et al. Structural basis and specificity of human otubain 1-mediated deubiquitination. Biochem J. 2009;418:379-90 pubmed publisher
  15. Zeng F, Xu J, Harris R. Nedd4 mediates ErbB4 JM-a/CYT-1 ICD ubiquitination and degradation in MDCK II cells. FASEB J. 2009;23:1935-45 pubmed publisher
    ..These studies indicate that Nedd4 mediates ErbB4 CYT-1 ICD ubiquitination and degradation, and the prevention of both WW binding and PI3 kinase activity are required for ErbB4 nuclear translocation. ..
  16. Walseng E, Furuta K, Bosch B, Weih K, Matsuki Y, Bakke O, et al. Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells. Proc Natl Acad Sci U S A. 2010;107:20465-70 pubmed publisher
    ..Thus, the cellular distribution and stability of surface pMHC-II in DCs is regulated by ubiquitin-dependent degradation of internalized pMHC-II. ..
  17. Ho K, Zhou Z, She Y, Chun A, Cyr T, Yang X. Itch E3 ubiquitin ligase regulates large tumor suppressor 1 stability [corrected]. Proc Natl Acad Sci U S A. 2011;108:4870-5 pubmed publisher
    ..Taking these data together, our study identifies E3 ubiquitin ligase Itch as a unique negative regulator of LATS1 and presents a possibility of targeting LATS1/Itch interaction as a therapeutic strategy in cancer. ..
  18. Wild P, Farhan H, McEwan D, Wagner S, Rogov V, Brady N, et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science. 2011;333:228-33 pubmed publisher
    ..We propose that phosphorylation of autophagy receptors might be a general mechanism for regulation of cargo-selective autophagy. ..
  19. Skaug B, Chen J, Du F, He J, Ma A, Chen Z. Direct, noncatalytic mechanism of IKK inhibition by A20. Mol Cell. 2011;44:559-71 pubmed publisher
    ..Our results suggest a noncatalytic mechanism of IKK inhibition by A20 and a means by which polyubiquitin chains can specify a signaling outcome. ..
  20. Zhang L, Zhou F, Drabsch Y, Gao R, Snaar Jagalska B, Mickanin C, et al. USP4 is regulated by AKT phosphorylation and directly deubiquitylates TGF-? type I receptor. Nat Cell Biol. 2012;14:717-26 pubmed publisher
    ..Moreover, AKT-induced breast cancer cell migration was inhibited by USP4 depletion and T?RI kinase inhibition. Our results uncover USP4 as an important determinant for crosstalk between TGF-? and AKT signalling pathways. ..
  21. Mishra A, Maheshwari M, Chhangani D, Fujimori Tonou N, Endo F, Joshi A, et al. E6-AP association promotes SOD1 aggresomes degradation and suppresses toxicity. Neurobiol Aging. 2013;34:1310.e11-23 pubmed publisher
    ..These data suggest that enhancing the activity of E6-AP ubiquitin ligase might be a viable therapeutic strategy to eliminate mutant SOD1-mediated toxicity in ALS. ..
  22. Lorick K, Jensen J, Fang S, Ong A, Hatakeyama S, Weissman A. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc Natl Acad Sci U S A. 1999;96:11364-9 pubmed
    ..These findings suggest that a large number of RING finger-containing proteins, with otherwise diverse structures and functions, may play previously unappreciated roles in modulating protein levels via ubiquitination. ..
  23. Angers A, Ramjaun A, McPherson P. The HECT domain ligase itch ubiquitinates endophilin and localizes to the trans-Golgi network and endosomal system. J Biol Chem. 2004;279:11471-9 pubmed
    ..We have thus identified endophilin A1 as a substrate for the endosome-localized ubiquitin ligase itch. This interaction may be involved in ubiquitin-mediated sorting mechanisms operating at the level of endosomes. ..
  24. Zhang X, Srinivasan S, Lingrel J. WWP1-dependent ubiquitination and degradation of the lung Krüppel-like factor, KLF2. Biochem Biophys Res Commun. 2004;316:139-48 pubmed
    ..Our experiments demonstrate for the first time that WWP1 promotes ubiquitination and degradation of KLF2 and is not involved in the ubiquitin-transfer reaction. ..
  25. Marteijn J, van Emst L, Erpelinck Verschueren C, Nikoloski G, Menke A, de Witte T, et al. The E3 ubiquitin-protein ligase Triad1 inhibits clonogenic growth of primary myeloid progenitor cells. Blood. 2005;106:4114-23 pubmed
    ..We conclude that proteasomal degradation of proteins that are ubiquitinated by Triad1 affects the clonogenic growth of primary myeloid progenitor cells...
  26. Plans V, Scheper J, Soler M, Loukili N, Okano Y, Thomson T. The RING finger protein RNF8 recruits UBC13 for lysine 63-based self polyubiquitylation. J Cell Biochem. 2006;97:572-82 pubmed
    ..Thus, our screening reveals new potential regulators of non-canonical polyubiquitylation. ..
  27. REYES TURCU F, Horton J, Mullally J, Heroux A, Cheng X, Wilkinson K. The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of unanchored ubiquitin. Cell. 2006;124:1197-208 pubmed
    ..These data suggest that binding the ubiquitin C terminus may be necessary for the function of other proteins. ..
  28. Bhandari D, Trejo J, Benovic J, Marchese A. Arrestin-2 interacts with the ubiquitin-protein isopeptide ligase atrophin-interacting protein 4 and mediates endosomal sorting of the chemokine receptor CXCR4. J Biol Chem. 2007;282:36971-9 pubmed
    ..Taken together, our data suggest that the AIP4.arrestin-2 complex functions on endosomes to regulate sorting of CXCR4 into the degradative pathway. ..
  29. Wagner S, Carpentier I, Rogov V, Kreike M, Ikeda F, Lohr F, et al. Ubiquitin binding mediates the NF-kappaB inhibitory potential of ABIN proteins. Oncogene. 2008;27:3739-45 pubmed publisher
    ..Taken together, these data illustrate an important role for ubiquitin binding in the negative regulation of NF-kappaB signaling by ABINs and identify UBAN as a novel UBD. ..
  30. Wang T, Yin L, Cooper E, Lai M, Dickey S, Pickart C, et al. Evidence for bidentate substrate binding as the basis for the K48 linkage specificity of otubain 1. J Mol Biol. 2009;386:1011-23 pubmed publisher
    ..Bidentate binding may be a general strategy used to achieve linkage-specific deubiquitination. ..
  31. Ernst R, Mueller B, Ploegh H, Schlieker C. The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER. Mol Cell. 2009;36:28-38 pubmed publisher
    ..The assignment of a p97-associated ubiquitin processing function to YOD1 adds to our understanding of p97's role in the dislocation process. ..
  32. Gao S, Alarcon C, Sapkota G, Rahman S, Chen P, Goerner N, et al. Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling. Mol Cell. 2009;36:457-68 pubmed publisher
    ..Previously identified as a regulator of renal sodium channels, Nedd4L is shown here to play a broader role as a general modulator of Smad turnover during TGF-beta signal transduction. ..
  33. Kuiken H, Egan D, Laman H, Bernards R, Beijersbergen R, Dirac A. Identification of F-box only protein 7 as a negative regulator of NF-kappaB signalling. J Cell Mol Med. 2012;16:2140-9 pubmed publisher
    ..F-box protein only 7 binds to, and mediates ubiquitin conjugation to cIAP1 and TRAF2, resulting in decreased RIP1 ubiquitination and lowered NF-?B signalling activity. ..
  34. Fan C, Lum M, Xu C, Black J, Wang X. Ubiquitin-dependent regulation of phospho-AKT dynamics by the ubiquitin E3 ligase, NEDD4-1, in the insulin-like growth factor-1 response. J Biol Chem. 2013;288:1674-84 pubmed publisher
    ..This study reveals a novel mechanism by which a specific E3 ligase is required for ubiquitin-dependent control of pAKT dynamics in a ligand-specific manner. ..
  35. Saito S, Murata T, Kanda T, Isomura H, Narita Y, Sugimoto A, et al. Epstein-Barr virus deubiquitinase downregulates TRAF6-mediated NF-?B signaling during productive replication. J Virol. 2013;87:4060-70 pubmed publisher
  36. Shenoy S, McDonald P, Kohout T, Lefkowitz R. Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin. Science. 2001;294:1307-13 pubmed
  37. Jehn B, Dittert I, Beyer S, von der Mark K, Bielke W. c-Cbl binding and ubiquitin-dependent lysosomal degradation of membrane-associated Notch1. J Biol Chem. 2002;277:8033-40 pubmed
    ..Our data suggest a regulatory mechanism down-regulating Notch1 protein levels already at the cellular surface, possibly with consequences for Notch-dependent signal transduction during terminal differentiation processes. ..
  38. Laplantine E, Fontan E, Chiaravalli J, Lopez T, Lakisic G, Veron M, et al. NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain. EMBO J. 2009;28:2885-95 pubmed publisher
    ..We also demonstrate that the recently described binding of NEMO to linear poly-ubiquitin chains is dependent on the NOA alone and does not require the presence of the ZF. ..
  39. Yamazaki K, Gohda J, Kanayama A, Miyamoto Y, Sakurai H, Yamamoto M, et al. Two mechanistically and temporally distinct NF-kappaB activation pathways in IL-1 signaling. Sci Signal. 2009;2:ra66 pubmed publisher
    ..Therefore, we propose that the cooperative activation of NF-kappaB by two mechanistically and temporally distinct MEKK3-dependent pathways that diverge at TRAF6 critically contributes to immune and inflammatory systems. ..
  40. Marinis J, Homer C, McDonald C, Abbott D. A novel motif in the Crohn's disease susceptibility protein, NOD2, allows TRAF4 to down-regulate innate immune responses. J Biol Chem. 2011;286:1938-50 pubmed publisher
    ..This work identifies a novel negative regulator of NOD2 signaling. Additionally, it defines a TRAF4 binding motif within NOD2 involved in termination of innate immune signaling responses. ..
  41. Giandomenico V, Simonsson M, Grönroos E, Ericsson J. Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors. Mol Cell Biol. 2003;23:2587-99 pubmed
    ..Thus, our studies define acetylation-dependent stabilization of transcription factors as a novel mechanism for coactivators to regulate gene expression. ..
  42. Zhang D, Hannink M. Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol. 2003;23:8137-51 pubmed
    ..We propose that Keap1 is a component of a novel E3 ubiquitin ligase complex that is specifically targeted for inhibition by both chemopreventive agents and oxidative stress. ..
  43. Kuratomi G, Komuro A, Goto K, Shinozaki M, Miyazawa K, Miyazono K, et al. NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-beta (transforming growth factor-beta) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta type I receptor. Biochem J. 2005;386:461-70 pubmed
  44. Hong F, Sekhar K, Freeman M, Liebler D. Specific patterns of electrophile adduction trigger Keap1 ubiquitination and Nrf2 activation. J Biol Chem. 2005;280:31768-75 pubmed
    ..These results suggest that Keap1 adduction triggers a switching of Cul3-dependent ubiquitination from Nrf2 to Keap1, leading to Nrf2 activation. ..
  45. Sorkina T, Miranda M, Dionne K, Hoover B, Zahniser N, Sorkin A. RNA interference screen reveals an essential role of Nedd4-2 in dopamine transporter ubiquitination and endocytosis. J Neurosci. 2006;26:8195-205 pubmed
    ..A new mechanistic model of DAT endocytosis is proposed whereby the PKC-induced ubiquitination of DAT mediated by Nedd4-2 leads to interaction of DAT with adaptor proteins in coated pits and acceleration of DAT endocytosis. ..
  46. Winter M, Sombroek D, Dauth I, Moehlenbrink J, Scheuermann K, Crone J, et al. Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR. Nat Cell Biol. 2008;10:812-24 pubmed publisher
    ..Our results provide a molecular framework for HIPK2 regulation in unstressed and damaged cells. ..
  47. Langelier C, Sandrin V, Eckert D, Christensen D, Chandrasekaran V, Alam S, et al. Biochemical characterization of a recombinant TRIM5alpha protein that restricts human immunodeficiency virus type 1 replication. J Virol. 2008;82:11682-94 pubmed publisher
  48. Todi S, Winborn B, Scaglione K, Blount J, Travis S, Paulson H. Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin-3. EMBO J. 2009;28:372-82 pubmed publisher
    ..Ataxin-3 is the first reported DUB in which ubiquitination directly regulates catalytic activity. We propose a new function for protein ubiquitination in regulating the activity of certain DUBs and perhaps other enzymes...
  49. Okamoto K, Taya Y, Nakagama H. Mdmx enhances p53 ubiquitination by altering the substrate preference of the Mdm2 ubiquitin ligase. FEBS Lett. 2009;583:2710-4 pubmed publisher
    ..Alteration of the substrate specificity via binding to Mdmx may contribute to efficient ubiquitination and inactivation of p53 by Mdm2. ..
  50. Sato Y, Yoshikawa A, Yamashita M, Yamagata A, Fukai S. Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by NZF domains of TAB2 and TAB3. EMBO J. 2009;28:3903-9 pubmed publisher
    ..We therefore propose a mechanism for the recognition of Lys 63-linked polyubiquitin chains by TAB2 and TAB3 NZF domains in which diubiquitin units are specifically recognized by a single NZF domain. ..
  51. Ning S, Pagano J. The A20 deubiquitinase activity negatively regulates LMP1 activation of IRF7. J Virol. 2010;84:6130-8 pubmed publisher
    ..Thus, A20 negatively regulates LMP1-stimulated IRF7 ubiquitination and activity in EBV latency, and its DUB activity is indispensable for this function. Finally, we discussed the regulation and function of IRFs in EBV latency. ..
  52. Feng L, Wang J, Chen J. The Lys63-specific deubiquitinating enzyme BRCC36 is regulated by two scaffold proteins localizing in different subcellular compartments. J Biol Chem. 2010;285:30982-8 pubmed publisher
    ..Together, these results suggest that scaffold proteins not only participate in the regulation of BRCC36 activity but also determine its subcellular localization and cellular functions. ..
  53. Chen R, Li M, Zhang Y, Zhou Q, Shu H. The E3 ubiquitin ligase MARCH8 negatively regulates IL-1?-induced NF-?B activation by targeting the IL1RAP coreceptor for ubiquitination and degradation. Proc Natl Acad Sci U S A. 2012;109:14128-33 pubmed publisher
    ..Our findings suggest that MARCH8-mediated polyubiquitination and degradation of IL1RAP is an important mechanism for negative regulation of IL-1?-induced signaling pathways. ..
  54. Zhang J, Bai D, Ma X, Guan J, Zheng X. hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway by controlling NEDDylation of ribosomal protein S14. Oncogene. 2014;33:246-54 pubmed publisher
    ..These findings suggest that hCINAP is an important regulator of RP-HDM2-p53 pathway and a potential anticancer drug target. ..
  55. Pornillos O, Alam S, Rich R, Myszka D, Davis D, Sundquist W. Structure and functional interactions of the Tsg101 UEV domain. EMBO J. 2002;21:2397-406 pubmed
    ..These studies provide a structural framework for understanding how Tsg101 mediates the protein-protein interactions required for HIV budding and VPS. ..
  56. Bartee E, Mansouri M, Hovey Nerenberg B, Gouveia K, Fruh K. Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins. J Virol. 2004;78:1109-20 pubmed
  57. Liani E, Eyal A, Avraham E, Shemer R, Szargel R, Berg D, et al. Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease. Proc Natl Acad Sci U S A. 2004;101:5500-5 pubmed
    ..In vitro experiments show that SIAH-2 monoubiquitylates alpha-synuclein. Further evidence that SIAH proteins may play a role in inclusion formation comes from the demonstration of SIAH immunoreactivity in Lewy bodies of PD patients. ..
  58. Zeng S, Xu Z, Lipkowitz S, Longley J. Regulation of stem cell factor receptor signaling by Cbl family proteins (Cbl-b/c-Cbl). Blood. 2005;105:226-32 pubmed
    ..The activated KIT in turn induces phosphorylation and activation of Cbl proteins. The Cbl proteins then bind and direct the degradation of activated KIT, leading to down-regulation of KIT signaling. ..
  59. Yu X, Minter Dykhouse K, Malureanu L, Zhao W, Zhang D, Merkle C, et al. Chfr is required for tumor suppression and Aurora A regulation. Nat Genet. 2005;37:401-6 pubmed
    ..Collectively, our data suggest that Chfr is a tumor suppressor and ensures chromosomal stability by controlling the expression levels of key mitotic proteins such as Aurora A. ..
  60. van der Horst A, de Vries Smits A, Brenkman A, van Triest M, van den Broek N, Colland F, et al. FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol. 2006;8:1064-73 pubmed
    ..Our results demonstrate a novel mechanism of FOXO regulation and indicate that USP7 has an important role in regulating FOXO-mediated stress responses. ..
  61. Uldrijan S, Pannekoek W, Vousden K. An essential function of the extreme C-terminus of MDM2 can be provided by MDMX. EMBO J. 2007;26:102-12 pubmed
    ..Interestingly, the E3 activity of C-terminal point mutants of MDM2 can also be supported by interaction with wild-type MDMX, suggesting that MDMX can directly contribute to E3 function. ..
  62. Avraham E, Rott R, Liani E, Szargel R, Engelender S. Phosphorylation of Parkin by the cyclin-dependent kinase 5 at the linker region modulates its ubiquitin-ligase activity and aggregation. J Biol Chem. 2007;282:12842-50 pubmed
    ..Phosphorylation by Cdk5 may contribute to the accumulation of toxic Parkin substrates and decrease the ability of dopaminergic cells to cope with toxic insults in Parkinson disease. ..
  63. Rondou P, Haegeman G, Vanhoenacker P, Van Craenenbroeck K. BTB Protein KLHL12 targets the dopamine D4 receptor for ubiquitination by a Cul3-based E3 ligase. J Biol Chem. 2008;283:11083-96 pubmed publisher
  64. Guardavaccaro D, Frescas D, Dorrello N, Peschiaroli A, Multani A, Cardozo T, et al. Control of chromosome stability by the beta-TrCP-REST-Mad2 axis. Nature. 2008;452:365-9 pubmed publisher
    ..The high levels of REST or its truncated variants found in certain human tumours may contribute to cellular transformation by promoting genomic instability. ..
  65. Wu J, Huen M, Lu L, Ye L, Dou Y, Ljungman M, et al. Histone ubiquitination associates with BRCA1-dependent DNA damage response. Mol Cell Biol. 2009;29:849-60 pubmed publisher
    ..Taken together, our results suggest that ubiquitinated histones H2A and H2B may recruit the BRCA1 complex to DNA damage lesions on the chromatin. ..
  66. Jin Z, Li Y, Pitti R, Lawrence D, Pham V, Lill J, et al. Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell. 2009;137:721-35 pubmed publisher
    ..These results identify a mechanism that positively controls apoptosis signaling by polyubiquitination and aggregation of a key initiator caspase. ..
  67. Broglie P, Matsumoto K, Akira S, Brautigan D, Ninomiya Tsuji J. Transforming growth factor beta-activated kinase 1 (TAK1) kinase adaptor, TAK1-binding protein 2, plays dual roles in TAK1 signaling by recruiting both an activator and an inhibitor of TAK1 kinase in tumor necrosis factor signaling pathway. J Biol Chem. 2010;285:2333-9 pubmed publisher
    ..Our results indicate that TAB2 not only activates TAK1 but also plays an essential role in the deactivation of TAK1 by recruiting PP6 through a polyubiquitin chain-dependent mechanism. ..
  68. Nicastro G, Todi S, Karaca E, Bonvin A, Paulson H, Pastore A. Understanding the role of the Josephin domain in the PolyUb binding and cleavage properties of ataxin-3. PLoS ONE. 2010;5:e12430 pubmed publisher
    ..Site 1, which is close to the active site, is indispensable for cleavage. Our studies open the way to understand better the cellular function of ataxin-3 and its link to pathology. ..
  69. Ye Y, Akutsu M, Reyes Turcu F, Enchev R, Wilkinson K, Komander D. Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21. EMBO Rep. 2011;12:350-7 pubmed publisher
    ..We also rationalize the inability of USP21 to target NEDD8 and identify differences that allow USPs to distinguish between structurally related modifications. ..
  70. Hu H, Brittain G, Chang J, Puebla Osorio N, Jin J, Zal A, et al. OTUD7B controls non-canonical NF-?B activation through deubiquitination of TRAF3. Nature. 2013;494:371-4 pubmed publisher
    ..These findings establish OTUD7B as a crucial regulator of signal-induced non-canonical NF-?B activation and indicate a mechanism of immune regulation that involves OTUD7B-mediated deubiquitination and stabilization of TRAF3. ..
  71. Qi J, Tripathi M, Mishra R, Sahgal N, Fazli L, Fazil L, et al. The E3 ubiquitin ligase Siah2 contributes to castration-resistant prostate cancer by regulation of androgen receptor transcriptional activity. Cancer Cell. 2013;23:332-46 pubmed publisher
    ..Notably, Siah2 expression is markedly increased in human CRPCs. Collectively, we find that selective regulation of AR transcriptional activity by the ubiquitin ligase Siah2 is important for CRPC development. ..
  72. Rao N, Ghosh A, Ota S, Zhou P, Reddi A, Hakezi K, et al. The non-receptor tyrosine kinase Syk is a target of Cbl-mediated ubiquitylation upon B-cell receptor stimulation. EMBO J. 2001;20:7085-95 pubmed
    ..Altogether, our results support an essential role for Cbl ubiquitin ligase activity in the negative regulation of Syk, and establish that ubiquitylation provides a mechanism of Cbl-mediated negative regulation of cytoplasmic targets. ..
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