Tripartite Motif 8 (TRIM8) Modulates TNFα- and IL-1β-triggered NF-κB Activation by Targeting TAK1 for K63-linked Polyubiquitination

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2011 Nov 16

PMID 22084099

Citations 104

Authors

Qi Li

Jie Yan

Ai-Ping Mao

Chao Li

Yong Ran

Hong-Bing Shu

Yan-Yi Wang

Affiliations

Soon will be listed here.

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.

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