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Tripartite motif 8 (TRIM8) modulates TNFÎ±- and IL-1Î²âtriggered NF-ÎºB activation by targeting TAK1 for K63-linked polyubiquitination
- Li, Qi, Yan, Jie, Mao, Ai-Ping, Li, Chao, Ran, Yong, Shu, Hong-Bing, Wang, Yan-Yi
- Proceedings of the National Academy of Sciences of the United States of America 2011 v.108 no.48 pp. 19341-19346
- immune response, interleukin-1, proteins, serine, threonine, transforming growth factor beta, tumor necrosis factor-alpha
- 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-Î± (TNFÎ±) and interleukin-1Î² (IL-1Î²)âtriggered NF-ÎºB activation. Overexpression of TRIM8 activated NF-ÎºB and potentiated TNFÎ±- and IL-1Î²âinduced activation of NF-ÎºB, whereas knockdown of TRIM8 had opposite effects. Coimmunoprecipitations indicated that TRIM8 interacted with TGFÎ² activated kinase 1 (TAK1), a serine/threonine kinase essential for TNFÎ±- and IL-Î²âinduced NF-ÎºB activation. Furthermore, we found that TRIM8 mediated K63-linked polyubiquitination of TAK1 triggered by TNFÎ± and IL-1Î². Our findings demonstrate that TRIM8 serves as a critical regulator of TNFÎ±- and IL-1Î²âinduced NF-ÎºB activation by mediating K63-linked polyubiquitination of TAK1.