Tripartite motif 8 (TRIM8) modulates TNFα- and IL-1β-triggered NF-κB activation by targeting TAK1 for K63-linked polyubiquitination.
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.
Mesh Terms:
Animals, Carrier Proteins, Cell Line, DNA, Complementary, Gene Knockdown Techniques, Humans, Immunoblotting, Immunoprecipitation, Interleukin-1beta, Luciferases, MAP Kinase Kinase Kinases, Mice, NF-kappa B, Nerve Tissue Proteins, Plasmids, RNA Interference, Real-Time Polymerase Chain Reaction, Tumor Necrosis Factor-alpha, Ubiquitination
Animals, Carrier Proteins, Cell Line, DNA, Complementary, Gene Knockdown Techniques, Humans, Immunoblotting, Immunoprecipitation, Interleukin-1beta, Luciferases, MAP Kinase Kinase Kinases, Mice, NF-kappa B, Nerve Tissue Proteins, Plasmids, RNA Interference, Real-Time Polymerase Chain Reaction, Tumor Necrosis Factor-alpha, Ubiquitination
Proc. Natl. Acad. Sci. U.S.A.
Date: Nov. 29, 2011
PubMed ID: 22084099
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