期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 48, 页码 19341-19346出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1110946108
关键词
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资金
- Ministry of Science and Technology of China [2012CB910200]
- National Natural Science Foundation of China [30921001, 91029302, 31170792]
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-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta)-triggered NF-kappa B activation. Overexpression of TRIM8 activated NF-kappa B and potentiated TNF alpha- and IL-1 beta-induced activation of NF-kappa B, whereas knockdown of TRIM8 had opposite effects. Coimmunoprecipitations indicated that TRIM8 interacted with TGF beta activated kinase 1 (TAK1), a serine/threonine kinase essential for TNF alpha- and IL-beta-induced NF-kappa B activation. Furthermore, we found that TRIM8 mediated K63-linked polyubiquitination of TAK1 triggered by TNF alpha and IL-1 beta. Our findings demonstrate that TRIM8 serves as a critical regulator of TNF alpha- and IL-1 beta-induced NF-kappa B activation by mediating K63-linked polyubiquitination of TAK1.
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