TRAF6

Summary

Gene Symbol: TRAF6
Description: TNF receptor associated factor 6
Alias: MGC:3310, RNF85, TNF receptor-associated factor 6, E3 ubiquitin-protein ligase TRAF6, RING finger protein 85, RING-type E3 ubiquitin transferase TRAF6, TNF receptor-associated factor 6, E3 ubiquitin protein ligase, interleukin-1 signal transducer
Species: human
Products:     TRAF6

Top Publications

  1. Deng L, Wang C, Spencer E, Yang L, Braun A, You J, et al. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell. 2000;103:351-61 pubmed
    b>TRAF6 is a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. We have purified a heterodimeric protein complex that links TRAF6 to IKK activation...
  2. Ninomiya Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K. The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature. 1999;398:252-6 pubmed
    ..cascade that leads to activation of the transcription factor NF-kappaB and is relayed through the protein TRAF6 and a succession of kinase enzymes, including NF-kappaB-inducing kinase (NIK) and I kappaB kinases (IKKs)...
  3. Seibenhener M, Babu J, Geetha T, Wong H, Krishna N, Wooten M. Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol. 2004;24:8055-68 pubmed
    ..Altogether, our results support the hypothesis that p62 may act as a critical ubiquitin chain-targeting factor that shuttles substrates for proteasomal degradation. ..
  4. Tao M, Scacheri P, Marinis J, Harhaj E, Matesic L, Abbott D. ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory signaling pathways. Curr Biol. 2009;19:1255-63 pubmed publisher
    ..These findings suggest that ITCH helps regulate NOD2-dependent signal transduction pathways and, as such, may be involved in the pathogenesis of NOD2-mediated inflammatory disease. ..
  5. Kishida S, Sanjo H, Akira S, Matsumoto K, Ninomiya Tsuji J. TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway. Genes Cells. 2005;10:447-54 pubmed
    ..adaptor that links TAK1 to an upstream signaling intermediate, tumor necrosis factor receptor-associated factor 6 (TRAF6). Recently, ubiquitination of TRAF6 was shown to play an essential role in the activation of TAK1...
  6. Martin P, Diaz Meco M, Moscat J. The signaling adapter p62 is an important mediator of T helper 2 cell function and allergic airway inflammation. EMBO J. 2006;25:3524-33 pubmed
    ....
  7. Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, et al. TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway. Mol Cell. 2000;5:649-58 pubmed
    ..we report the identification of TAB2, a novel intermediate in the IL-1 pathway that functionally links TAK1 to TRAF6. Expression of TAB2 induces JNK and NF-kappaB activation, whereas a dominant-negative mutant TAB2 impairs their ..
  8. Muroi M, Tanamoto K. TRAF6 distinctively mediates MyD88- and IRAK-1-induced activation of NF-kappaB. J Leukoc Biol. 2008;83:702-7 pubmed
    ..it is known that expression of these proteins leads to the activation of NF-kappaB in a TNFR-associated factor 6 (TRAF6)-dependent manner...
  9. Liu X, Wei B, Shi H, Shan Y, Wang C. Tom70 mediates activation of interferon regulatory factor 3 on mitochondria. Cell Res. 2010;20:994-1011 pubmed publisher
    ..Collectively, our study characterizes Tom70 as a critical adaptor linking MAVS to TBK1/IRF3, revealing that mitochondrion is evolutionarily integrated with innate immunity. ..
  10. Yoshida R, Takaesu G, Yoshida H, Okamoto F, Yoshioka T, Choi Y, et al. TRAF6 and MEKK1 play a pivotal role in the RIG-I-like helicase antiviral pathway. J Biol Chem. 2008;283:36211-20 pubmed publisher
    ..b>TRAF6 and the downstream kinase TAK1 have been shown to be essential for the production of proinflammatory cytokines ..

Detail Information

Publications62

  1. Deng L, Wang C, Spencer E, Yang L, Braun A, You J, et al. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell. 2000;103:351-61 pubmed
    b>TRAF6 is a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. We have purified a heterodimeric protein complex that links TRAF6 to IKK activation...
  2. Ninomiya Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K. The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature. 1999;398:252-6 pubmed
    ..cascade that leads to activation of the transcription factor NF-kappaB and is relayed through the protein TRAF6 and a succession of kinase enzymes, including NF-kappaB-inducing kinase (NIK) and I kappaB kinases (IKKs)...
  3. Seibenhener M, Babu J, Geetha T, Wong H, Krishna N, Wooten M. Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol. 2004;24:8055-68 pubmed
    ..Altogether, our results support the hypothesis that p62 may act as a critical ubiquitin chain-targeting factor that shuttles substrates for proteasomal degradation. ..
  4. Tao M, Scacheri P, Marinis J, Harhaj E, Matesic L, Abbott D. ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory signaling pathways. Curr Biol. 2009;19:1255-63 pubmed publisher
    ..These findings suggest that ITCH helps regulate NOD2-dependent signal transduction pathways and, as such, may be involved in the pathogenesis of NOD2-mediated inflammatory disease. ..
  5. Kishida S, Sanjo H, Akira S, Matsumoto K, Ninomiya Tsuji J. TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway. Genes Cells. 2005;10:447-54 pubmed
    ..adaptor that links TAK1 to an upstream signaling intermediate, tumor necrosis factor receptor-associated factor 6 (TRAF6). Recently, ubiquitination of TRAF6 was shown to play an essential role in the activation of TAK1...
  6. Martin P, Diaz Meco M, Moscat J. The signaling adapter p62 is an important mediator of T helper 2 cell function and allergic airway inflammation. EMBO J. 2006;25:3524-33 pubmed
    ....
  7. Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, et al. TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway. Mol Cell. 2000;5:649-58 pubmed
    ..we report the identification of TAB2, a novel intermediate in the IL-1 pathway that functionally links TAK1 to TRAF6. Expression of TAB2 induces JNK and NF-kappaB activation, whereas a dominant-negative mutant TAB2 impairs their ..
  8. Muroi M, Tanamoto K. TRAF6 distinctively mediates MyD88- and IRAK-1-induced activation of NF-kappaB. J Leukoc Biol. 2008;83:702-7 pubmed
    ..it is known that expression of these proteins leads to the activation of NF-kappaB in a TNFR-associated factor 6 (TRAF6)-dependent manner...
  9. Liu X, Wei B, Shi H, Shan Y, Wang C. Tom70 mediates activation of interferon regulatory factor 3 on mitochondria. Cell Res. 2010;20:994-1011 pubmed publisher
    ..Collectively, our study characterizes Tom70 as a critical adaptor linking MAVS to TBK1/IRF3, revealing that mitochondrion is evolutionarily integrated with innate immunity. ..
  10. Yoshida R, Takaesu G, Yoshida H, Okamoto F, Yoshioka T, Choi Y, et al. TRAF6 and MEKK1 play a pivotal role in the RIG-I-like helicase antiviral pathway. J Biol Chem. 2008;283:36211-20 pubmed publisher
    ..b>TRAF6 and the downstream kinase TAK1 have been shown to be essential for the production of proinflammatory cytokines ..
  11. Yoshida Y, Kumar A, Koyama Y, Peng H, Arman A, Boch J, et al. Interleukin 1 activates STAT3/nuclear factor-kappaB cross-talk via a unique TRAF6- and p65-dependent mechanism. J Biol Chem. 2004;279:1768-76 pubmed
    ..bind p65 homodimers, is shown to be uniquely dependent upon signal transduction through the carboxyl terminus of TRAF6. Furthermore, STAT3 and p65 are shown to physically interact, in vivo, and this interaction appears to inhibit the ..
  12. Wooten M, Geetha T, Seibenhener M, Babu J, Diaz Meco M, Moscat J. The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination. J Biol Chem. 2005;280:35625-9 pubmed
    ..1/p62 is a scaffolding protein with several interaction modules that include a PB1 dimerization domain, a TRAF6 (tumor necrosis factor receptor-associated factor 6) binding site, and a ubiquitin-associating (UBA) domain...
  13. Lappalainen M, Paavola Sakki P, Halme L, Turunen U, Helio T, Farkkila M, et al. Screening of tumor necrosis factor receptor-associated factor 6 as a candidate gene for inflammatory bowel disease. Scand J Gastroenterol. 2006;41:424-9 pubmed
    ..region contains a functional IBD candidate gene coding for tumor necrosis factor receptor-associated factor 6 (TRAF6), a signal transducer regulating innate and adaptive immunity as well as bone homeostasis...
  14. Jiang Z, Ninomiya Tsuji J, Qian Y, Matsumoto K, Li X. Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol. Mol Cell Biol. 2002;22:7158-67 pubmed
    ..We now find that the phosphorylated IRAK in turn recruits TRAF6 to the receptor complex (complex I), which differs from the previous concept that IRAK interacts with TRAF6 after ..
  15. Wang K, Galson D, Auron P. TRAF6 is autoinhibited by an intramolecular interaction which is counteracted by trans-ubiquitination. J Cell Biochem. 2010;110:763-71 pubmed publisher
    ..Investigation of the mechanism by which TRAF6 is activated has demonstrated that two critical domains of the molecule required for activation and downstream ..
  16. Fitzgerald K, Palsson McDermott E, Bowie A, Jefferies C, Mansell A, Brady G, et al. Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature. 2001;413:78-83 pubmed
    ..Mal associates with TLR-4. Mal is therefore an adapter in TLR-4 signal transduction. ..
  17. Lamothe B, Besse A, Campos A, Webster W, Wu H, Darnay B. Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. J Biol Chem. 2007;282:4102-12 pubmed
    Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is a key mediator in proximal signaling of the interleukin-1/Toll-like receptor and the TNF receptor superfamily...
  18. Hinz M, Stilmann M, Arslan S, Khanna K, Dittmar G, Scheidereit C. A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-κB activation. Mol Cell. 2010;40:63-74 pubmed publisher
    ..Through a TRAF-binding motif, ATM activates TRAF6, resulting in Ubc13-mediated K63-linked polyubiquitin synthesis and cIAP1 recruitment...
  19. Wan J, Zhang W, Wu L, Bai T, Zhang M, Lo K, et al. BS69, a specific adaptor in the latent membrane protein 1-mediated c-Jun N-terminal kinase pathway. Mol Cell Biol. 2006;26:448-56 pubmed
    ..potently activates the cellular c-Jun N-terminal kinase (JNK) pathway by sequentially engaging an unknown adaptor, TRAF6, TAB1/TAK1, and JNKKs...
  20. An J, Mo D, Liu H, Veena M, Srivatsan E, Massoumi R, et al. Inactivation of the CYLD deubiquitinase by HPV E6 mediates hypoxia-induced NF-kappaB activation. Cancer Cell. 2008;14:394-407 pubmed publisher
    ..Given the established role of NF-kappaB in human carcinogenesis, these findings provide a potential molecular/viral link between hypoxia and the adverse clinical outcomes observed in HPV-associated malignancies. ..
  21. Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N, et al. The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. Nat Cell Biol. 2008;10:1199-207 pubmed publisher
    ..However, the molecular mechanisms for its activation are unknown. Here we report that the ubiquitin ligase (E3) TRAF6 interacts with a consensus motif present in TbetaRI...
  22. Lin S, Chung J, Lamothe B, Rajashankar K, Lu M, Lo Y, et al. Molecular basis for the unique deubiquitinating activity of the NF-kappaB inhibitor A20. J Mol Biol. 2008;376:526-40 pubmed publisher
    ..domain of A20 is a deubiquitinating enzyme (DUB) for Lys63-linked polyubiquitinated signaling mediators such as TRAF6 and RIP, its C-terminal domain is a ubiquitin ligase (E3) for Lys48-linked degradative polyubiquitination of the ..
  23. Conze D, Wu C, Thomas J, Landstrom A, Ashwell J. Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation. Mol Cell Biol. 2008;28:3538-47 pubmed publisher
    ..Stimulation through the interleukin-1 receptor (IL-1R) and some Toll-like receptors (TLRs) induces ubiquitination of TRAF6 and IRAK-1, signaling components required for NF-kappaB and mitogen-activated protein kinase activation...
  24. Mansell A, Brint E, Gould J, O Neill L, Hertzog P. Mal interacts with tumor necrosis factor receptor-associated factor (TRAF)-6 to mediate NF-kappaB activation by toll-like receptor (TLR)-2 and TLR4. J Biol Chem. 2004;279:37227-30 pubmed
    ..In this study, we have identified a putative TRAF6 interaction site in Mal but not in MyD88 and we demonstrate that Mal can be co-immunoprecipitated with TRAF6...
  25. Zhou L, Ma Q, Shi H, Huo K. NUMBL interacts with TRAF6 and promotes the degradation of TRAF6. Biochem Biophys Res Commun. 2010;392:409-14 pubmed publisher
    Tumor necrosis factor-associated factor 6 (TRAF6) is an essential adaptor protein for IL-1R or TLR-mediated NF-kappaB signaling pathway activation...
  26. Shi C, Kehrl J. TRAF6 and A20 regulate lysine 63-linked ubiquitination of Beclin-1 to control TLR4-induced autophagy. Sci Signal. 2010;3:ra42 pubmed publisher
    ..We found that tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-mediated, Lys(63) (K63)-linked ubiquitination of Beclin-1 is critical for TLR4-triggered autophagy in macrophages...
  27. Megas C, Hatzivassiliou E, Yin Q, Marinopoulou E, Hadweh P, Vignali D, et al. Mutational analysis of TRAF6 reveals a conserved functional role of the RING dimerization interface and a potentially necessary but insufficient role of RING-dependent TRAF6 polyubiquitination towards NF-κB activation. Cell Signal. 2011;23:772-7 pubmed publisher
    b>TRAF6 is an E3 ubiquitin ligase that plays a pivotal role in the activation of NF-κB by innate and adaptive immunity stimuli...
  28. Kawai T, Sato S, Ishii K, Coban C, Hemmi H, Yamamoto M, et al. Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat Immunol. 2004;5:1061-8 pubmed
    ..Furthermore, the adaptor molecule TRAF6 also bound and activated IRF7. Ubiquitin ligase activity of TRAF6 was required for IRF7 activation...
  29. Evans P, Taylor E, Coadwell J, Heyninck K, Beyaert R, Kilshaw P. Isolation and characterization of two novel A20-like proteins. Biochem J. 2001;357:617-23 pubmed
    ..Co-immunoprecipitation studies indicated that TRAF6 was able to interact with both Cezanne and TRABID...
  30. Kobayashi N, Kadono Y, Naito A, Matsumoto K, Yamamoto T, Tanaka S, et al. Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis. EMBO J. 2001;20:1271-80 pubmed
    ..These kinases are thought to be activated by tumor necrosis factor receptor-associated factor 6 (TRAF6). However, molecular mechanisms by which TRAF6 activates various downstream kinases remain to be elucidated...
  31. 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
    ..in part, by the deubiquitination and inactivation of TNFR-associated factor 2 (TRAF2) and, to a lesser extent, TRAF6. These results indicate that CYLD is a negative regulator of the cytokine-mediated activation of NF-kappaB that is ..
  32. McCully R, Pomerantz J. The protein kinase C-responsive inhibitory domain of CARD11 functions in NF-kappaB activation to regulate the association of multiple signaling cofactors that differentially depend on Bcl10 and MALT1 for association. Mol Cell Biol. 2008;28:5668-86 pubmed publisher
    ..inhibitory domain (ID) that controls the association of CARD11 with multiple signaling cofactors, including Bcl10, TRAF6, TAK1, IKKgamma, and caspase-8, through an interaction that requires both the caspase recruitment domain (CARD) ..
  33. 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. ..
  34. Meng Q, Zheng M, Liu H, Song C, Zhang W, Yan J, et al. TRAF6 regulates proliferation, apoptosis, and invasion of osteosarcoma cell. Mol Cell Biochem. 2012;371:177-86 pubmed publisher
    b>TRAF6, a unique tumor necrosis factor receptor-associated factor (TRAF) family member, possesses a unique receptor-binding specificity that results in its crucial role as the signaling mediator for TNF receptor superfamily and ..
  35. Schwandner R, Yamaguchi K, Cao Z. Requirement of tumor necrosis factor receptor-associated factor (TRAF)6 in interleukin 17 signal transduction. J Exp Med. 2000;191:1233-40 pubmed
    ..In embryonic fibroblasts (EFs) derived from TRAF6 knockout mice, IL-17 failed to activate the IkappaB kinases (IKKs) and JNK...
  36. Shembade N, Harhaj N, Yamamoto M, Akira S, Harhaj E. The human T-cell leukemia virus type 1 Tax oncoprotein requires the ubiquitin-conjugating enzyme Ubc13 for NF-kappaB activation. J Virol. 2007;81:13735-42 pubmed
    ..Collectively, our results reveal that Ubc13 is essential for Tax ubiquitination, its interaction with NEMO, and Tax-mediated NF-kappaB activation...
  37. Zhao J, Kong H, Li H, Huang B, Yang M, Zhu C, et al. IRF-8/interferon (IFN) consensus sequence-binding protein is involved in Toll-like receptor (TLR) signaling and contributes to the cross-talk between TLR and IFN-gamma signaling pathways. J Biol Chem. 2006;281:10073-80 pubmed
    ..Furthermore, co-immunoprecipitation experiments show that IRF-8 physically interacts with TRAF6 at a binding site between amino acid residues 356 and 305 of IRF-8...
  38. Kovalenko A, Chable Bessia C, Cantarella G, Israel A, Wallach D, Courtois G. The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination. Nature. 2003;424:801-5 pubmed
    ..Truncations of CYLD found in cylindromatosis result in reduced enzymatic activity, indicating a link between impaired deubiquitination of CYLD substrates and human pathophysiology. ..
  39. Ha U, Lim J, Kim H, Wu W, Jin S, Xu H, et al. MKP1 regulates the induction of MUC5AC mucin by Streptococcus pneumoniae pneumolysin by inhibiting the PAK4-JNK signaling pathway. J Biol Chem. 2008;283:30624-31 pubmed publisher
    ..Moreover pneumolysin also selectively induced expression of MKP1 via a TLR4-dependent MyD88-TRAF6-ERK signaling pathway, which inhibited the PAK4-JNK signaling pathway, thereby leading to up-regulation of MUC5AC ..
  40. Feng Y, Longmore G. The LIM protein Ajuba influences interleukin-1-induced NF-kappaB activation by affecting the assembly and activity of the protein kinase Czeta/p62/TRAF6 signaling complex. Mol Cell Biol. 2005;25:4010-22 pubmed
    ..in response to interleukin-1 (IL-1) and tumor necrosis factor signaling through the formation of an aPKC/p62/TRAF6 multiprotein signaling complex...
  41. Takaoka A, Yanai H, Kondo S, Duncan G, Negishi H, Mizutani T, et al. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature. 2005;434:243-9 pubmed
    ..We also provide evidence that IRF-5 interacts with and is activated by MyD88 and TRAF6, and that TLR activation results in the nuclear translocation of IRF-5 to activate cytokine gene transcription...
  42. Lee J, Lee H, Lee E, Jang S, Kim H, Yoon J, et al. Down syndrome candidate region-1 protein interacts with Tollip and positively modulates interleukin-1 receptor-mediated signaling. Biochim Biophys Acta. 2009;1790:1673-80 pubmed publisher
    ..signaling by analyzing interaction between DSCR1-1S and the IL-1R pathway components Tollip, IRAK-1, and TRAF6. Co-immunoprecipitation analyses of HEK293 cells revealed that DSCR1-1S interacted with Tollip, an IRAK-1 ..
  43. Emmerich C, Ordureau A, Strickson S, Arthur J, Pedrioli P, Komander D, et al. Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains. Proc Natl Acad Sci U S A. 2013;110:15247-52 pubmed publisher
    ..Our study may help to resolve the debate about the relative importance of K63-pUb and M1-pUb chains in activating the canonical IKK complex. ..
  44. LeBlanc P, Yeretssian G, Rutherford N, Doiron K, Nadiri A, Zhu L, et al. Caspase-12 modulates NOD signaling and regulates antimicrobial peptide production and mucosal immunity. Cell Host Microbe. 2008;3:146-57 pubmed publisher
    ..Mechanistically, caspase-12 binds to Rip2, displacing Traf6 from the signaling complex, inhibiting its ubiquitin ligase activity, and blunting NF-kappaB activation...
  45. Xu L, Wang Y, Han K, Li L, Zhai Z, Shu H. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell. 2005;19:727-40 pubmed
    ..Our data also indicate that VISA interacts with TRIF and TRAF6 and mediates bifurcation of the TLR3-triggered NF-kappaB and IRF-3 activation pathways...
  46. Wong B, Besser D, Kim N, Arron J, Vologodskaia M, Hanafusa H, et al. TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol Cell. 1999;4:1041-9 pubmed
    ..TRANCE activates the antiapoptotic serine/threonine kinase Akt/PKB through a signaling complex involving c-Src and TRAF6. A deficiency in c-Src or addition of Src family kinase inhibitors blocks TRANCE-mediated PKB activation in ..
  47. Mukundan L, Bishop G, Head K, Zhang L, Wahl L, Suttles J. TNF receptor-associated factor 6 is an essential mediator of CD40-activated proinflammatory pathways in monocytes and macrophages. J Immunol. 2005;174:1081-90 pubmed
    ..However, ligation of a CD40 mutant lacking a functional TRAF6 binding site did not initiate inflammatory cytokine production, and this mutant was found to be defective in CD40-..
  48. Xia X, Treanor J, Senaldi G, Khare S, Boone T, Kelley M, et al. TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation. J Exp Med. 2000;192:137-43 pubmed
    ..The identification and characterization of the receptor for TALL-1 provides useful information for the development of a treatment for B cell-mediated autoimmune diseases such as systemic lupus erythematosus. ..
  49. Sato S, Sugiyama M, Yamamoto M, Watanabe Y, Kawai T, Takeda K, et al. Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-li. J Immunol. 2003;171:4304-10 pubmed
    ..TNF receptor-associated factor (TRAF)6 interacted with TRIF through the TRAF domain of TRAF6 and TRAF6-binding motifs found in the N-terminal portion of TRIF...
  50. Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L, et al. SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol. 2003;4:920-7 pubmed
    ..Finally, biochemical analysis indicated that SIGIRR binds to the TLR-IL-1R signaling components in a ligand-dependent way. Our data show that SIGIRR functions as a biologically important modulator of TLR-IL-1R signaling. ..
  51. Petroski M, Zhou X, Dong G, Daniel Issakani S, Payan D, Huang J. Substrate modification with lysine 63-linked ubiquitin chains through the UBC13-UEV1A ubiquitin-conjugating enzyme. J Biol Chem. 2007;282:29936-45 pubmed
    ..we have developed an in vitro system to examine the activity of the ubiquitin-conjugating enzyme UBC13-UEV1A with TRAF6 in which TRAF6 serves as both a ubiquitin ligase and substrate for modification...
  52. Starczynowski D, Lockwood W, Delehouzee S, Chari R, Wegrzyn J, Fuller M, et al. TRAF6 is an amplified oncogene bridging the RAS and NF-κB pathways in human lung cancer. J Clin Invest. 2011;121:4095-105 pubmed publisher
    ..Within this region, only TNF receptor-associated factor 6 (TRAF6) exhibited concomitant mRNA overexpression and gene amplification in lung cancers...
  53. Mu Y, Sundar R, Thakur N, Ekman M, Gudey S, Yakymovych M, et al. TRAF6 ubiquitinates TGFβ type I receptor to promote its cleavage and nuclear translocation in cancer. Nat Commun. 2011;2:330 pubmed publisher
    ..TβRI is associated with the ubiquitin ligase tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)...
  54. Pype S, Declercq W, Ibrahimi A, Michiels C, Van Rietschoten J, Dewulf N, et al. TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that inhibits nuclear factor-kappa B activation. J Biol Chem. 2000;275:18586-93 pubmed
    ..The region of the CD40 cytoplasmic domain that is required for TTRAP association overlaps with the TRAF6 recognition motif...
  55. Mochida Y, Takeda K, Saitoh M, Nishitoh H, Amagasa T, Ninomiya Tsuji J, et al. ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction. J Biol Chem. 2000;275:32747-52 pubmed
    ..Overexpression of ASK1 inhibits IL-1-, TRAF6-, or TAK1-induced, but not NF-kappaB-inducing kinase-induced, NF-kappaB activation...
  56. Bradley J, Pober J. Tumor necrosis factor receptor-associated factors (TRAFs). Oncogene. 2001;20:6482-91 pubmed
    ..are thought to be important regulators of cell death and cellular responses to stress, and TRAF2, TRAF5 and TRAF6 have been demonstrated to mediate activation of NF-kappaB and JNK...
  57. Li S, Zheng H, Mao A, Zhong B, Li Y, Liu Y, et al. Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6. J Biol Chem. 2010;285:4291-7 pubmed publisher
    ..Coimmunoprecipitations indicated OTUB1 and -2 interacted with TRAF3 and TRAF6, two E3 ubiquitin ligases required for virus-triggered IRF3 and NF-kappaB activation, respectively...
  58. Kollewe C, Mackensen A, Neumann D, Knop J, Cao P, Li S, et al. Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling. J Biol Chem. 2004;279:5227-36 pubmed
    ..of IRAK-1 from the upstream adapters MyD88 and Tollip but leaves its interaction with the downstream adapter TRAF6 unaffected...
  59. Xia Z, Sun L, Chen X, Pineda G, Jiang X, Adhikari A, et al. Direct activation of protein kinases by unanchored polyubiquitin chains. Nature. 2009;461:114-9 pubmed publisher
    b>TRAF6 is a ubiquitin ligase that is essential for the activation of NF-kappaB and MAP kinases in several signalling pathways, including those emanating from the interleukin 1 and Toll-like receptors...
  60. Ishitani T, Takaesu G, Ninomiya Tsuji J, Shibuya H, Gaynor R, Matsumoto K. Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling. EMBO J. 2003;22:6277-88 pubmed
    ..TAB2, a TAK1-binding protein, is involved in IL-1-induced NF-kappaB activation by physically linking TAK1 to TRAF6. However, IL-1-induced activation of NF-kappaB is not impaired in TAB2-deficient embryonic fibroblasts...
  61. Seth R, Sun L, Ea C, Chen Z. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell. 2005;122:669-82 pubmed
    ..The transmembrane domain targets MAVS to the mitochondria, implicating a new role of mitochondria in innate immunity...
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