Tripartite motif 8 (TRIM8) modulates TNF?- and IL-1?-triggered NF-?B 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-? (TNF?) and interleukin-1? (IL-1?)-triggered NF-?B activation. Overexpression of TRIM8 activated NF-?B and potentiated TNF?- and IL-1?-induced activation of NF-?B, whereas knockdown of TRIM8 had opposite effects. Coimmunoprecipitations indicated that TRIM8 interacted with TGF? activated kinase 1 (TAK1), a serine/threonine kinase essential for TNF?- and IL-?-induced NF-?B activation. Furthermore, we found that TRIM8 mediated K63-linked polyubiquitination of TAK1 triggered by TNF? and IL-1?. Our findings demonstrate that TRIM8 serves as a critical regulator of TNF?- and IL-1?-induced NF-?B activation by mediating K63-linked polyubiquitination of TAK1.

SUBMITTER: Li Q 

PROVIDER: S-EPMC3228454 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature