title: Tripartite motif 8 (TRIM8) modulates TNFα- and IL-1β-triggered NF-κB activation by targeting TAK1 for K63-linked polyubiquitination.
abstract: The tripartite motif (TRIM)-containing proteins are a family of proteins that have been known to be involved in divergent biological processes, including important roles in immune responses through regulating various signaling pathways. In this study, we identified a member of the TRIM family, TRIM8, as a positive regulator of tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β)-triggered NF-κB activation. Overexpression of TRIM8 activated NF-κB and potentiated TNFα- and IL-1β-induced activation of NF-κB, whereas knockdown of TRIM8 had opposite effects. Coimmunoprecipitations indicated that TRIM8 interacted with TGFβ activated kinase 1 (TAK1), a serine/threonine kinase essential for TNFα- and IL-β-induced NF-κB activation. Furthermore, we found that TRIM8 mediated K63-linked polyubiquitination of TAK1 triggered by TNFα and IL-1β. Our findings demonstrate that TRIM8 serves as a critical regulator of TNFα- and IL-1β-induced NF-κB activation by mediating K63-linked polyubiquitination of TAK1.
authors.affiliation: College of Life Sciences,  Wuhan University, Wuhan 430072,  China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Mao
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Ran
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
authors.forename: Yan-Yi
authors.initials: YY
authors.lastname: Wang
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D053583:Interleukin-1beta / Q000378:metabolism*; D008156:Luciferases; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D054875:Ubiquitination; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D053583:Interleukin-1beta; D008156:Luciferases; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha; D000099151:MAP Kinase Kinase Kinase 7; C418604:TRIM8 protein, human
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