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. 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. ..
  9. Junn E, Lee S, Suhr U, Mouradian M. Parkin accumulation in aggresomes due to proteasome impairment. J Biol Chem. 2002;277:47870-7 pubmed
    ..We propose that the process of Lewy body formation may be akin to that of aggresome-like structures. The tendency of wild-type Parkin to aggregate and form inclusions may have implications for the pathogenesis of sporadic PD. ..

More Information

Publications330 found, 100 shown here

  1. Shim M, Smart R. Lithium stabilizes the CCAAT/enhancer-binding protein alpha (C/EBPalpha) through a glycogen synthase kinase 3 (GSK3)-independent pathway involving direct inhibition of proteasomal activity. J Biol Chem. 2003;278:19674-81 pubmed
    ..These results demonstrate C/EBPalpha is degraded via a ubiquitin-dependent proteasomal pathway, and LiCl stabilizes C/EBPalpha through a GSK3-independent pathway involving direct inhibition of proteasome activity. ..
  2. Trompouki E, Hatzivassiliou E, Tsichritzis T, Farmer H, Ashworth A, Mosialos G. CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members. Nature. 2003;424:793-6 pubmed
    ..These results indicate that CYLD is a negative regulator of the cytokine-mediated activation of NF-kappaB that is required for appropriate cellular homeostasis of skin appendages. ..
  3. Wang Q, Goh A, Howley P, Walters K. Ubiquitin recognition by the DNA repair protein hHR23a. Biochemistry. 2003;42:13529-35 pubmed
    ..HHR23 proteins are hypothesized to link ubiquitin to S5a, and we provide direct evidence that hHR23 could form a ternary complex with ubiquitin and S5a. ..
  4. Peschard P, Ishiyama N, Lin T, Lipkowitz S, Park M. A conserved DpYR motif in the juxtamembrane domain of the Met receptor family forms an atypical c-Cbl/Cbl-b tyrosine kinase binding domain binding site required for suppression of oncogenic activation. J Biol Chem. 2004;279:29565-71 pubmed
    ..The DpYR motif is conserved in other members of the Met RTK family but is not present in previously identified c-Cbl-binding proteins, identifying DpYR as a new binding motif for c-Cbl and Cbl-b. ..
  5. Hu M, Li P, Song L, Jeffrey P, Chenova T, Wilkinson K, et al. Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14. EMBO J. 2005;24:3747-56 pubmed
    ..These structural observations, in conjunction with biochemical characterization, identify important regulatory mechanisms for USP14. ..
  6. Chen C, Sun X, Guo P, Dong X, Sethi P, Cheng X, et al. Human Kruppel-like factor 5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells. J Biol Chem. 2005;280:41553-61 pubmed
    ..These findings not only established WWP1 as an E3 ubiquitin ligase for KLF5, they also further implicated the KLF5 pathway in human carcinogenesis. ..
  7. Nasr R, Chiari E, El Sabban M, Mahieux R, Kfoury Y, Abdulhay M, et al. Tax ubiquitylation and sumoylation control critical cytoplasmic and nuclear steps of NF-kappaB activation. Blood. 2006;107:4021-9 pubmed
    ..Thus, ubiquitylation and sumoylation of the same residues of Tax regulate 2 essential steps controlling NF-kappaB activation, demonstrating how these posttranslational modifications can cooperate to promote Tax-induced transformation...
  8. Renatus M, Parrado S, D Arcy A, Eidhoff U, Gerhartz B, Hassiepen U, et al. Structural basis of ubiquitin recognition by the deubiquitinating protease USP2. Structure. 2006;14:1293-302 pubmed
    ..As several of those molecules are found at identical positions in the previously solved USP7/ubiquitin-aldehyde complex structure, we suggest a general mechanism of water-mediated ubiquitin recognition by USPs. ..
  9. Pak Y, Glowacka W, Bruce M, Pham N, Rotin D. Transport of LAPTM5 to lysosomes requires association with the ubiquitin ligase Nedd4, but not LAPTM5 ubiquitination. J Cell Biol. 2006;175:631-45 pubmed
    ..These results demonstrate a novel mechanism by which the ubiquitin-ligase Nedd4, via interactions with GGA3 and cargo (LAPTM5), regulates cargo trafficking to the lysosome without requiring cargo ubiquitination. ..
  10. Stamenova S, French M, He Y, Francis S, Kramer Z, Hicke L. Ubiquitin binds to and regulates a subset of SH3 domains. Mol Cell. 2007;25:273-84 pubmed
    ..We conclude that a subset of SH3 domains constitutes a distinct type of ubiquitin-binding domain and that ubiquitin binding can negatively regulate interaction of SH3 domains with canonical proline-rich ligands. ..
  11. Schweitzer K, Bozko P, Dubiel W, Naumann M. CSN controls NF-kappaB by deubiquitinylation of IkappaBalpha. EMBO J. 2007;26:1532-41 pubmed
    ..We propose that the CSN controls both CRL activity and stability of the CRL substrate IkappaBalpha. In consequence, basal and signal-induced CRL-dependent turnover of IkappaBalpha is precisely adapted to specific cellular needs. ..
  12. Pelzer C, Kassner I, Matentzoglu K, Singh R, Wollscheid H, Scheffner M, et al. UBE1L2, a novel E1 enzyme specific for ubiquitin. J Biol Chem. 2007;282:23010-4 pubmed
    ..The UBE1L2 mRNA is most abundantly expressed in the testis, suggesting an organ-specific regulation of ubiquitin activation. ..
  13. Wei S, Yang H, Chuang H, Yang J, Kulp S, Lu P, et al. A novel mechanism by which thiazolidinediones facilitate the proteasomal degradation of cyclin D1 in cancer cells. J Biol Chem. 2008;283:26759-70 pubmed publisher
    ..Moreover, we obtained evidence that this beta-TrCP-dependent degradation takes part in controlling cyclin D1 turnover when cancer cells undergo glucose starvation, which endows physiological relevance to this novel mechanism. ..
  14. Zhang L, Park C, Wu J, Kim H, Liu W, Fujita T, et al. Proteolysis of Rad17 by Cdh1/APC regulates checkpoint termination and recovery from genotoxic stress. EMBO J. 2010;29:1726-37 pubmed publisher
    ..The findings provide an insight into how the proteolysis of Rad17 by Cdh1/APC regulates the termination of checkpoint signalling and the recovery from genotoxic stress. ..
  15. Deveraux Q, Ustrell V, Pickart C, Rechsteiner M. A 26 S protease subunit that binds ubiquitin conjugates. J Biol Chem. 1994;269:7059-61 pubmed
    ..Thus, proteins conjugated to polymers of ubiquitin may be selected for degradation by a single subunit of the 26 S protease complex. ..
  16. von der Lehr N, Johansson S, Wu S, Bahram F, Castell A, Cetinkaya C, et al. The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription. Mol Cell. 2003;11:1189-200 pubmed
    ..The results suggest that Skp2 is a transcriptional cofactor for c-Myc and indicates a close relationship between transcription activation and transcription factor ubiquitination. ..
  17. Yang H, Wen Y, Chen C, Lozano G, Lee M. 14-3-3 sigma positively regulates p53 and suppresses tumor growth. Mol Cell Biol. 2003;23:7096-107 pubmed
    ..These results defined an important p53 regulatory loop and suggested that 14-3-3 sigma expression can be considered for therapeutic intervention in cancers. ..
  18. Song B, DeBose Boyd R. Ubiquitination of 3-hydroxy-3-methylglutaryl-CoA reductase in permeabilized cells mediated by cytosolic E1 and a putative membrane-bound ubiquitin ligase. J Biol Chem. 2004;279:28798-806 pubmed
  19. Raasi S, Varadan R, Fushman D, Pickart C. Diverse polyubiquitin interaction properties of ubiquitin-associated domains. Nat Struct Mol Biol. 2005;12:708-14 pubmed
    ..Conversely, non-UBA sequences can modulate the interaction properties of a UBA domain. ..
  20. House C, Hancock N, Möller A, Cromer B, Fedorov V, Bowtell D, et al. Elucidation of the substrate binding site of Siah ubiquitin ligase. Structure. 2006;14:695-701 pubmed
    ..Mutagenesis of Siah at sites of interaction also abrogates both in vitro peptide binding and destabilization of a known Siah target. ..
  21. Maine G, Mao X, Komarck C, Burstein E. COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase. EMBO J. 2007;26:436-47 pubmed
    ..Our data uncover that ubiquitination and degradation of NF-kappaB subunits by this COMMD1-containing ubiquitin ligase is a novel and critical mechanism of regulation of NF-kappaB-mediated transcription. ..
  22. Wang Q, Li L, Ye Y. Inhibition of p97-dependent protein degradation by Eeyarestatin I. J Biol Chem. 2008;283:7445-54 pubmed publisher
    ..Interestingly, p97-associated deubiquitination is also involved in degradation of a soluble substrate. Our analyses establish a role for a novel deubiquitinating process in proteasome-dependent protein turnover. ..
  23. Xiao H, Qian W, Staschke K, Qian Y, Cui G, Deng L, et al. Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NF kappaB activation. J Biol Chem. 2008;283:14654-64 pubmed publisher
    ..Taken together, our results suggest that Pellino 3b acts as a negative regulator for IL-1 signaling by regulating IRAK degradation through its ubiquitin protein ligase activity. ..
  24. Schlehe J, Lutz A, Pilsl A, Lämmermann K, Grgur K, Henn I, et al. Aberrant folding of pathogenic Parkin mutants: aggregation versus degradation. J Biol Chem. 2008;283:13771-9 pubmed publisher
  25. Chang M, Jin W, Sun S. Peli1 facilitates TRIF-dependent Toll-like receptor signaling and proinflammatory cytokine production. Nat Immunol. 2009;10:1089-95 pubmed publisher
    ..Our findings suggest that Peli1 is a ubiquitin ligase needed for the transmission of TRIF-dependent TLR signals. ..
  26. Ashida H, Kim M, Schmidt Supprian M, Ma A, Ogawa M, Sasakawa C. A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response. Nat Cell Biol. 2010;12:66-73; sup pp 1-9 pubmed publisher
    ..As NEMO is essential for NF-kappaB activation, we propose that the polyubiquitylation and degradation of NEMO during Shigella infection is a new bacterial strategy to modulate host inflammatory responses. ..
  27. Li W, You L, Cooper J, Schiavon G, Pepe Caprio A, Zhou L, et al. Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. Cell. 2010;140:477-90 pubmed publisher
    ..We propose that Merlin suppresses tumorigenesis by translocating to the nucleus to inhibit CRL4(DCAF1). ..
  28. Tsang Y, Lamb A, Romero Gallo J, Huang B, Ito K, Peek R, et al. Helicobacter pylori CagA targets gastric tumor suppressor RUNX3 for proteasome-mediated degradation. Oncogene. 2010;29:5643-50 pubmed publisher
    ..Our studies identify RUNX3 as a novel cellular target of H. pylori CagA and also reveal a mechanism by which CagA functions as an oncoprotein by blocking the activity of gastric tumor suppressor RUNX3. ..
  29. Todi S, Scaglione K, Blount J, Basrur V, Conlon K, Pastore A, et al. Activity and cellular functions of the deubiquitinating enzyme and polyglutamine disease protein ataxin-3 are regulated by ubiquitination at lysine 117. J Biol Chem. 2010;285:39303-13 pubmed publisher
  30. Wu S, Wang W, Kong X, Congdon L, Yokomori K, Kirschner M, et al. Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression. Genes Dev. 2010;24:2531-42 pubmed publisher
    ..Collectively, we elucidated the molecular mechanisms that control PR-Set7 protein levels during mitosis, and demonstrated that its orchestrated regulation is important for normal mitotic progression. ..
  31. Tsuchida T, Zou J, Saitoh T, Kumar H, Abe T, Matsuura Y, et al. The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA. Immunity. 2010;33:765-76 pubmed publisher
    ..Taken together, these results indicate that TRIM56 is an interferon-inducible E3 ubiquitin ligase that modulates STING to confer double-stranded DNA-mediated innate immune responses. ..
  32. Huang O, Ma X, Yin J, Flinders J, Maurer T, Kayagaki N, et al. Phosphorylation-dependent activity of the deubiquitinase DUBA. Nat Struct Mol Biol. 2012;19:171-5 pubmed publisher
    ..Phosphoactivation of DUBA represents an unprecedented mode of protease regulation and a clear link between two major cellular signal transduction systems: phosphorylation and ubiquitin modification. ..
  33. Eichhorn P, Rodón L, Gonzàlez Juncà A, Dirac A, Gili M, Martínez Sáez E, et al. USP15 stabilizes TGF-? receptor I and promotes oncogenesis through the activation of TGF-? signaling in glioblastoma. Nat Med. 2012;18:429-35 pubmed publisher
    ..Our results show that USP15 regulates the TGF-? pathway and is a key factor in glioblastoma pathogenesis. ..
  34. Wu J, Zhang X, Zhang L, Wu C, Rezaeian A, Chan C, et al. Skp2 E3 ligase integrates ATM activation and homologous recombination repair by ubiquitinating NBS1. Mol Cell. 2012;46:351-61 pubmed publisher
    ..Our results provide molecular insights into how Skp2 and the MRN complex coordinate to activate ATM, and identify Skp2-mediatetd NBS1 ubiquitination as a vital event for ATM activation in response to DNA damage. ..
  35. Centore R, Yazinski S, Tse A, Zou L. Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response. Mol Cell. 2012;46:625-35 pubmed publisher
    ..Thus, as a "reader" of ubiquitylated PCNA, Spartan promotes an unexpected feed-forward loop to enhance PCNA ubiquitylation and translesion DNA synthesis. ..
  36. Kwak Y, Wang B, Li J, Wang R, Deng Q, Diao S, et al. Upregulation of the E3 ligase NEDD4-1 by oxidative stress degrades IGF-1 receptor protein in neurodegeneration. J Neurosci. 2012;32:10971-81 pubmed
    ..Together, our work identifies a novel molecular mechanism for ROS-upregulated NEDD4-1 and the subsequently reduced IGF-1R? signaling in neurodegeneration. ..
  37. Shenoy S, Lefkowitz R. Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination. J Biol Chem. 2003;278:14498-506 pubmed
    ..Thus the ubiquitination status of beta-arrestin determines the stability of the receptor-beta-arrestin complex as well as the trafficking pattern of beta-arrestin. ..
  38. Prag G, Lee S, Mattera R, Arighi C, Beach B, Bonifacino J, et al. Structural mechanism for ubiquitinated-cargo recognition by the Golgi-localized, gamma-ear-containing, ADP-ribosylation-factor-binding proteins. Proc Natl Acad Sci U S A. 2005;102:2334-9 pubmed
    ..This ability highlights the GAT domain as a hub for interactions with multiple partners in trafficking. ..
  39. Zhu G, Wu C, Zhao Y, Ashwell J. Optineurin negatively regulates TNFalpha- induced NF-kappaB activation by competing with NEMO for ubiquitinated RIP. Curr Biol. 2007;17:1438-43 pubmed
    ..These results reveal a physiologic role for optineurin in dampening TNFalpha signaling, and this role might provide an explanation for its association with glaucoma. ..
  40. Schmidt B, Watts R, Aridor M, Frizzell R. Cysteine string protein promotes proteasomal degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) by increasing its interaction with the C terminus of Hsp70-interacting protein and promoting CFTR ubiquitylation. J Biol Chem. 2009;284:4168-78 pubmed publisher
    ..These findings indicate that Csp not only regulates the exit of CFTR from the ER, but that this action is accompanied by Hsc70/Hsp70 and CHIP-mediated CFTR degradation. ..
  41. Shimoji T, Murakami K, Sugiyama Y, Matsuda M, Inubushi S, Nasu J, et al. Identification of annexin A1 as a novel substrate for E6AP-mediated ubiquitylation. J Cell Biochem. 2009;106:1123-35 pubmed publisher
    ..Our findings raise the possibility that E6AP may play a role in controlling the diverse functions of annexin A1 through the ubiquitin-proteasome pathway. ..
  42. Nabhan J, Pan H, Lu Q. Arrestin domain-containing protein 3 recruits the NEDD4 E3 ligase to mediate ubiquitination of the beta2-adrenergic receptor. EMBO Rep. 2010;11:605-11 pubmed publisher
    ..Our results establish ARRDC3 as an essential adaptor for beta2AR ubiquitination. ..
  43. Mimnaugh E, Chavany C, Neckers L. Polyubiquitination and proteasomal degradation of the p185c-erbB-2 receptor protein-tyrosine kinase induced by geldanamycin. J Biol Chem. 1996;271:22796-801 pubmed
  44. Tang E, Wang C, Xiong Y, Guan K. A role for NF-kappaB essential modifier/IkappaB kinase-gamma (NEMO/IKKgamma) ubiquitination in the activation of the IkappaB kinase complex by tumor necrosis factor-alpha. J Biol Chem. 2003;278:37297-305 pubmed
    ..Also, defective NEMO ubiquitination may be responsible for the impaired cellular NF-kappaB signaling found in patients with HED-ID. ..
  45. Kang J, Kang S, Kwon H, He W, Park S. Distinct interactions between ubiquitin and the SH3 domains involved in immune signaling. Biochim Biophys Acta. 2008;1784:1335-41 pubmed publisher
    ..Such results raise the possibility that the mechanistic variety of these immunologically relevant SH3 domains might contribute to their functional diversity. ..
  46. Bomberger J, Barnaby R, Stanton B. The deubiquitinating enzyme USP10 regulates the post-endocytic sorting of cystic fibrosis transmembrane conductance regulator in airway epithelial cells. J Biol Chem. 2009;284:18778-89 pubmed publisher
    ..These studies demonstrate a novel function for USP10 in facilitating the deubiquitination of CFTR in early endosomes and thereby enhancing the endocytic recycling of CFTR. ..
  47. Bianchi M, Crinelli R, Giacomini E, Carloni E, Magnani M. A potent enhancer element in the 5'-UTR intron is crucial for transcriptional regulation of the human ubiquitin C gene. Gene. 2009;448:88-101 pubmed publisher
    ..It is encoded by four genes, of which UbC is known to meet cell demand for ubiquitin in both basal and stressful conditions...
  48. Zucchelli S, Codrich M, Marcuzzi F, Pinto M, Vilotti S, Biagioli M, et al. TRAF6 promotes atypical ubiquitination of mutant DJ-1 and alpha-synuclein and is localized to Lewy bodies in sporadic Parkinson's disease brains. Hum Mol Genet. 2010;19:3759-70 pubmed publisher
    ..In human post-mortem brains of PD patients, TRAF6 protein colocalizes with aSYN in LBs. These results reveal a novel role for TRAF6 and for atypical ubiquitination in PD pathogenesis. ..
  49. Chen F, Zhang Z, Bower J, Lu Y, Leonard S, Ding M, et al. Arsenite-induced Cdc25C degradation is through the KEN-box and ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A. 2002;99:1990-5 pubmed
  50. Tateishi Y, Kawabe Y, Chiba T, Murata S, Ichikawa K, Murayama A, et al. Ligand-dependent switching of ubiquitin-proteasome pathways for estrogen receptor. EMBO J. 2004;23:4813-23 pubmed
    ..One pathway is necessary for the transactivation of the receptor and the other is involved in the quality control of the receptor. ..
  51. Finkbeiner M, Sawan C, Ouzounova M, Murr R, Herceg Z. HAT cofactor TRRAP mediates beta-catenin ubiquitination on the chromatin and the regulation of the canonical Wnt pathway. Cell Cycle. 2008;7:3908-14 pubmed
  52. Meijer I, van Leeuwen J. ERBB2 is a target for USP8-mediated deubiquitination. Cell Signal. 2011;23:458-67 pubmed publisher
    ..Our findings demonstrate that Usp8 is part of the ErbB2 endosomal trafficking pathway. ..
  53. Nakamura S, Roth J, Mukhopadhyay T. Multiple lysine mutations in the C-terminal domain of p53 interfere with MDM2-dependent protein degradation and ubiquitination. Mol Cell Biol. 2000;20:9391-8 pubmed
    ..Taken together, the data suggest that mutations in the putative acetylation sites of the p53 C-terminal domain interfere with ubiquitination, thereby regulating p53 degradation. ..
  54. West A, Moore D, Biskup S, Bugayenko A, Smith W, Ross C, et al. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A. 2005;102:16842-7 pubmed
    ..These results suggest a gain-of-function mechanism for LRRK2-linked disease with a central role for kinase activity in the development of PD. ..
  55. Levy D, Adamovich Y, Reuven N, Shaul Y. The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73. Cell Death Differ. 2007;14:743-51 pubmed
    ..Altogether, our findings attribute a central role to Yap1 in regulating p73 accumulation and function under DNA damage signaling. ..
  56. Yuan J, Luo K, Zhang L, Cheville J, Lou Z. USP10 regulates p53 localization and stability by deubiquitinating p53. Cell. 2010;140:384-96 pubmed publisher
    ..These findings reveal USP10 to be a novel regulator of p53, providing an alternative mechanism of p53 inhibition in cancers with wild-type p53. ..
  57. Russell R, Sufan R, Zhou B, Heir P, Bunda S, Sybingco S, et al. Loss of JAK2 regulation via a heterodimeric VHL-SOCS1 E3 ubiquitin ligase underlies Chuvash polycythemia. Nat Med. 2011;17:845-53 pubmed publisher
    ..These results show that VHL is a SOCS1-cooperative negative regulator of JAK2 and provide biochemical and preclinical support for JAK2-targeted therapy in individuals with Chuvash polycythemia. ..
  58. Hattori T, Isobe T, Abe K, Kikuchi H, Kitagawa K, Oda T, et al. Pirh2 promotes ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor p27Kip1. Cancer Res. 2007;67:10789-95 pubmed
    ..Overall, the results indicate that Pirh2 acts as a negative regulator of p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation. ..
  59. Otto T, Horn S, Brockmann M, Eilers U, Schüttrumpf L, Popov N, et al. Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell. 2009;15:67-78 pubmed publisher
    ..Aurora A interacts with both N-Myc and the SCF(Fbxw7) ubiquitin ligase that ubiquitinates N-Myc and counteracts degradation of N-Myc, thereby uncoupling N-Myc stability from growth factor-dependent signals. ..
  60. Wu Y, Deng J, Rychahou P, Qiu S, Evers B, Zhou B. Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion. Cancer Cell. 2009;15:416-28 pubmed publisher
    ..Our study provides a plausible mechanism for inflammation-induced metastasis. ..
  61. Endo A, Kitamura N, Komada M. Nucleophosmin/B23 regulates ubiquitin dynamics in nucleoli by recruiting deubiquitylating enzyme USP36. J Biol Chem. 2009;284:27918-23 pubmed publisher
    ..We conclude that nucleophosmin/B23 recruits USP36 to nucleoli, thereby serving as a platform for the regulation of nucleolar protein functions through ubiquitylation/deubiquitylation. ..
  62. Lee D, Kuo H, Liu M, Chou C, Xia W, Du Y, et al. KEAP1 E3 ligase-mediated downregulation of NF-kappaB signaling by targeting IKKbeta. Mol Cell. 2009;36:131-40 pubmed publisher
    ..Our results suggest that the dysregulation of KEAP1-mediated IKKbeta ubiquitination may contribute to tumorigenesis. ..
  63. Burstein E, Ganesh L, Dick R, van De Sluis B, Wilkinson J, Klomp L, et al. A novel role for XIAP in copper homeostasis through regulation of MURR1. EMBO J. 2004;23:244-54 pubmed
    ..These findings represent the first described phenotypic alteration in Xiap-deficient mice and demonstrate that XIAP can function through MURR1 to regulate copper homeostasis. ..
  64. Gottwein E, Jäger S, Habermann A, Kräusslich H. Cumulative mutations of ubiquitin acceptor sites in human immunodeficiency virus type 1 gag cause a late budding defect. J Virol. 2006;80:6267-75 pubmed
    ..This is consistent with Gag ubiquitination being functionally involved in a transient protein interaction network at the virus budding site. ..
  65. Schwamborn J, Berezikov E, Knoblich J. The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell. 2009;136:913-25 pubmed publisher
    ..TRIM32 is the mouse ortholog of Drosophila Brat and Mei-P26 and might be part of a protein family that regulates the balance between differentiation and proliferation in stem cell lineages. ..
  66. Malik R, Marchese A. Arrestin-2 interacts with the endosomal sorting complex required for transport machinery to modulate endosomal sorting of CXCR4. Mol Biol Cell. 2010;21:2529-41 pubmed publisher
    ..Our data suggest a mechanism whereby arrestin-2 via its interaction with STAM-1 modulates CXCR4 sorting by regulating the ubiquitination status of HRS. ..
  67. Maddika S, Kavela S, Rani N, Palicharla V, Pokorny J, Sarkaria J, et al. WWP2 is an E3 ubiquitin ligase for PTEN. Nat Cell Biol. 2011;13:728-33 pubmed publisher
    ..Functionally, we show that WWP2 controls cellular apoptosis and is required for tumorigenicity of cells. Collectively, our results reveal a functional E3 ubiquitin ligase for PTEN that plays a vital role in tumour-cell survival. ..
  68. Yang C, Li S, Wang M, Chang A, Liu Y, Zhao F, et al. PTEN suppresses the oncogenic function of AIB1 through decreasing its protein stability via mechanism involving Fbw7 alpha. Mol Cancer. 2013;12:21 pubmed publisher
  69. Komuro A, Imamura T, Saitoh M, Yoshida Y, Yamori T, Miyazono K, et al. Negative regulation of transforming growth factor-beta (TGF-beta) signaling by WW domain-containing protein 1 (WWP1). Oncogene. 2004;23:6914-23 pubmed
    ..Importantly, WWP1 and Smurfs were expressed in distinct patterns in human tissues and carcinoma cell lines, suggesting unique pathophysiological roles of WWP1 and Smurfs. ..
  70. Gack M, Shin Y, Joo C, Urano T, Liang C, Sun L, et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature. 2007;446:916-920 pubmed
    ..Thus, we demonstrate that TRIM25 E3 ubiquitin ligase induces the Lys 63-linked ubiquitination of RIG-I, which is crucial for the cytosolic RIG-I signalling pathway to elicit host antiviral innate immunity. ..
  71. Chen W, Sun Z, Wang X, Jiang T, Huang Z, Fang D, et al. Direct interaction between Nrf2 and p21(Cip1/WAF1) upregulates the Nrf2-mediated antioxidant response. Mol Cell. 2009;34:663-73 pubmed publisher
    ..Furthermore, the physiological significance of our findings was demonstrated in vivo using p21-deficient mice. ..
  72. Mizutani A, Saitoh M, Imamura T, Miyazawa K, Miyazono K. Arkadia complexes with clathrin adaptor AP2 and regulates EGF signalling. J Biochem. 2010;148:733-41 pubmed publisher
    ..Arkadia thus appears to regulate EGF signalling by modulating endocytosis of EGFR through interaction with AP2 complex. ..
  73. Sekhar K, Yan X, Freeman M. Nrf2 degradation by the ubiquitin proteasome pathway is inhibited by KIAA0132, the human homolog to INrf2. Oncogene. 2002;21:6829-34 pubmed
    ..Further, the observation that free Nrf2 is degraded by the ubiquitin proteasome pathway provides a potential mechanism by which ARE-dependent gene transcription is attenuated after induction. ..
  74. Dorrello N, Peschiaroli A, Guardavaccaro D, Colburn N, Sherman N, Pagano M. S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science. 2006;314:467-71 pubmed
    ..We propose that regulated degradation of PDCD4 in response to mitogens allows efficient protein synthesis and consequently cell growth. ..
  75. Varfolomeev E, Goncharov T, Fedorova A, Dynek J, Zobel K, Deshayes K, et al. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J Biol Chem. 2008;283:24295-9 pubmed publisher
    ..Therefore, c-IAP1 and c-IAP2 are required for TNFalpha-stimulated RIP1 ubiquitination and NF-kappaB activation. ..
  76. Shereda R, Machida Y, Machida Y. Human KIAA1018/FAN1 localizes to stalled replication forks via its ubiquitin-binding domain. Cell Cycle. 2010;9:3977-83 pubmed
    ..In addition, knockdown of FAN1 by RNA interference leads to increased sensitivity to interstrand crosslinking agents and accumulation of abnormal chromosomes. FAN1 may be an important new player in the maintenance of genome stability. ..
  77. Murdaca J, Treins C, Monthouël Kartmann M, Pontier Bres R, Kumar S, Van Obberghen E, et al. Grb10 prevents Nedd4-mediated vascular endothelial growth factor receptor-2 degradation. J Biol Chem. 2004;279:26754-61 pubmed
    ..In this study, we show that Grb10 acts as a positive regulator in VEGF-R2 signaling and protects VEGF-R2 from degradation by interacting with Nedd4, a component of the endocytic machinery. ..
  78. Kobayashi A, Kang M, Okawa H, Ohtsuji M, Zenke Y, Chiba T, et al. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol Cell Biol. 2004;24:7130-9 pubmed
    ..To our knowledge, Nrf2 and Keap1 are the first reported mammalian substrate and adaptor, respectively, of the Cul3-based E3 ligase system. ..
  79. Xia T, Dimitropoulou C, Zeng J, Antonova G, Snead C, Venema R, et al. Chaperone-dependent E3 ligase CHIP ubiquitinates and mediates proteasomal degradation of soluble guanylyl cyclase. Am J Physiol Heart Circ Physiol. 2007;293:H3080-7 pubmed
    ..This study reveals a new mechanism for the regulation of sGC, an important mediator of cellular and vascular function. ..
  80. Kirkin V, Lamark T, Sou Y, Bjørkøy G, Nunn J, Bruun J, et al. A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell. 2009;33:505-16 pubmed publisher
    ..We propose that NBR1 and p62 act as receptors for selective autophagosomal degradation of ubiquitinated targets. ..
  81. Jung C, Lim J, Choi Y, Kim D, Kang K, Noh S, et al. Enigma negatively regulates p53 through MDM2 and promotes tumor cell survival in mice. J Clin Invest. 2010;120:4493-506 pubmed publisher
    ..Our findings suggest a role for Enigma in tumorigenesis and uncover a mechanism whereby mitogens attenuate p53 antiproliferative activity through an SRF/Enigma/MDM2 pathway. ..
  82. Arnaud N, Dabo S, Akazawa D, Fukasawa M, Shinkai Ouchi F, Hugon J, et al. Hepatitis C virus reveals a novel early control in acute immune response. PLoS Pathog. 2011;7:e1002289 pubmed publisher
    ..Among those, ISG15 acts to negatively control the RIG-I/MAVS pathway, at the level of RIG-I ubiquitination.These data give novel insights in the machinery involved in the early events of innate immune response. ..
  83. Jo Y, Lee P, Sguigna P, DeBose Boyd R. Sterol-induced degradation of HMG CoA reductase depends on interplay of two Insigs and two ubiquitin ligases, gp78 and Trc8. Proc Natl Acad Sci U S A. 2011;108:20503-8 pubmed publisher
    ..Variations in the concentrations of any one of these proteins may account for differences in cell- and/or tissue-specific regulation of reductase degradation. ..
  84. Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, et al. Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J Biol Chem. 2001;276:12477-80 pubmed
    ..These results thus reveal a novel function of Smad7, i.e. induction of degradation of TbetaR-I through recruitment of an E3 ligase to the receptor. ..
  85. Cusson Hermance N, Khurana S, Lee T, Fitzgerald K, Kelliher M. Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation. J Biol Chem. 2005;280:36560-6 pubmed
    ..These studies suggest that Rip1 uses a similar, ubiquitin-dependent mechanism to activate IkappaB kinase-beta in response to TNF-alpha and TLR3 ligands. ..
  86. Geetha T, Kenchappa R, Wooten M, Carter B. TRAF6-mediated ubiquitination regulates nuclear translocation of NRIF, the p75 receptor interactor. EMBO J. 2005;24:3859-68 pubmed
    ..Finally, unlike wild-type NRIF, the K19R NRIF failed to reconstitute p75-mediated apoptosis in nrif-/- neurons. These results reveal a unique mechanism of p75 signaling and a novel role for K63-linked ubiquitin chains. ..
  87. Nakasato N, Ikeda K, Urano T, Horie Inoue K, Takeda S, Inoue S. A ubiquitin E3 ligase Efp is up-regulated by interferons and conjugated with ISG15. Biochem Biophys Res Commun. 2006;351:540-6 pubmed
    ..These data suggest that Efp is an IFN-responsive gene that potentially mediates IFN actions, involved in ISGylation and ubiquitination of proteins including Efp itself. ..
  88. Motegi A, Liaw H, Lee K, Roest H, Maas A, Wu X, et al. Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proc Natl Acad Sci U S A. 2008;105:12411-6 pubmed publisher
    ..Our results suggest that HLTF and SHPRH are functional homologues of yeast Rad5 that cooperatively mediate PCNA polyubiquitination and maintain genomic stability. ..
  89. Bomar M, Pai M, Tzeng S, Li S, Zhou P. Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase eta. EMBO Rep. 2007;8:247-51 pubmed
    ..The pol eta UBZ domain represents a novel member of the C(2)H(2) zinc finger family that interacts with ubiquitin to regulate translesion synthesis. ..
  90. Zhao W, Wang L, Zhang M, Wang P, Yuan C, Qi J, et al. Tripartite motif-containing protein 38 negatively regulates TLR3/4- and RIG-I-mediated IFN-? production and antiviral response by targeting NAP1. J Immunol. 2012;188:5311-8 pubmed publisher
    ..Therefore, our results demonstrate that TRIM38 is a negative regulator for TLR and RIG-I-mediated IFN-? production by targeting NAP1 for ubiquitination and subsequent proteasome-mediated degradation. ..
  91. Huang Z, Fujiwara K, Minamide R, Hasegawa K, Yoshikawa K. Necdin controls proliferation and apoptosis of embryonic neural stem cells in an oxygen tension-dependent manner. J Neurosci. 2013;33:10362-73 pubmed publisher
    ..These results suggest that oxygen tension regulates the necdin protein level in NSCs through HIF-2?-mediated proteasomal degradation to modulate their proliferation and apoptosis...
  92. Ettenberg S, Magnifico A, Cuello M, Nau M, Rubinstein Y, Yarden Y, et al. Cbl-b-dependent coordinated degradation of the epidermal growth factor receptor signaling complex. J Biol Chem. 2001;276:27677-84 pubmed
    ..Furthermore, the data demonstrate that Cbl-b mediates degradation of multiple proteins in the EGFR-signaling complex. ..