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Tripartite motif 8 (TRIM8) modulates TNFα- and IL-1β–triggered NF-κB activation by targeting TAK1 for K63-linked polyubiquitination

Author:
Li, Qi, Yan, Jie, Mao, Ai-Ping, Li, Chao, Ran, Yong, Shu, Hong-Bing, Wang, Yan-Yi
Source:
Proceedings of the National Academy of Sciences of the United States of America 2011 v.108 no.48 pp. 19341-19346
ISSN:
0027-8424
Subject:
immune response, interleukin-1, proteins, serine, threonine, transforming growth factor beta, tumor necrosis factor-alpha
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.
Agid:
401880