Tripartite motif 8 (TRIM8) modulates TNFα- and IL-1β-triggered NF-κB activation by targeting TAK1 for K63-linked polyubiquitination
Tripartite motif 8 (TRIM8) modulates TNFα- and IL-1β-triggered NF-κB activation by targeting TAK1 for K63-linked polyubiquitination
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DOI：
10.1073/pnas.1110946108
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发表时间：
2011-11-29
影响因子：
11.1
通讯作者：
Wang, Yan-Yi
中科院分区：
文献类型：
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作者：
Li, Qi;Yan, Jie;Wang, Yan-Yi
TRIM蛋白是一类参与多种生物学过程的蛋白质家族，通过调节多种信号通路在免疫应答中发挥重要作用。在这项研究中，我们鉴定了TRIM家族的一个成员TRIM 8，它是肿瘤坏死因子α（TNF α）和白细胞介素-1 β（IL-1 β）触发的NF-κ B激活的正调节因子。TRIM 8的过表达激活NF-κ B并增强TNF α和IL-1 β诱导的NF-κ B的激活，而TRIM 8的敲低具有相反的作用。免疫共沉淀表明TRIM 8与TGF β激活的激酶1（TAK 1）相互作用，TAK 1是TNF α和IL-β诱导的NF-κ B激活所必需的丝氨酸/苏氨酸激酶。此外，我们发现TRIM 8介导由TNF α和IL-1 β触发的TAK 1的K63连接的多聚泛素化。我们的研究结果表明，TRIM 8作为一个关键的调节TNF α和IL-1 β诱导的NF-κ B B激活介导的K63连接的多泛素化的TAK 1。
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.