TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway
TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway
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DOI：
10.1111/j.1365-2443.2005.00852.x
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发表时间：
2005-05-01
期刊：
影响因子：
2.1
通讯作者：
Ninomiya-Tsuji, J
中科院分区：
文献类型：
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作者：
Kishida, S;Sanjo, H;Ninomiya-Tsuji, J
TAK1丝裂原活化蛋白激酶激酶激酶通过介导JNK、p38和NF -κB的活化参与白细胞介素 - 1（IL - 1）信号通路。TAK1结合蛋白2（TAB2）先前被鉴定为一种衔接蛋白，它将TAK1与上游信号中间体肿瘤坏死因子受体相关因子6（TRAF6）连接起来。最近，已表明TRAF6的泛素化在TAK1的活化中起关键作用。然而，IL - 1诱导TRAF6泛素化的机制仍有待阐明。在此我们报道TAB2具有促进TRAF6泛素化的功能，从而介导IL - 1诱导的细胞事件。TAB2中一个保守的泛素结合结构域，即CUE结构域，对这一功能很重要。我们还发现TAB2促进TRAF6与下游激酶IκB激酶（IKK）的组装。这些结果表明TAB2作为一种多功能信号分子，既促进IL - 1依赖的TRAF6泛素化，又促进IL - 1信号复合物的组装。
TAK1 mitogen-activated protein kinase kinase kinase participates in the Interleukin-1 (IL-1) signaling pathway by mediating activation of JNK, p38, and NF-kappa B. TAK1-binding protein 2 (TAB2) was previously identified as an adaptor that links TAK1 to an upstream signaling intermediate, tumor necrosis factor receptor-associated factor 6 (TRAF6). Recently, ubiquitination of TRAF6 was shown to play an essential role in the activation of TAK1. However, the mechanism by which IL-1 induces TRAF6 ubiquitination remains to be elucidated. Here we report that TAB2 functions to facilitate TRAF6 ubiquitination and thereby mediates IL-1-induced cellular events. A conserved ubiquitin binding domain in TAB2, the CUE domain, is important for this function. We also found that TAB2 promotes the assembly of TRAF6 with a downstream kinase, I kappa B kinase (IKK). These results show that TAB2 acts as a multifunctional signaling molecule, facilitating both IL-1-dependent TRAF6 ubiquitination and assembly of the IL-1 signaling complex.