An F-box protein, FBXW5, negatively regulates TAK1 MAP3K in the IL-1β signaling pathway
An F-box protein, FBXW5, negatively regulates TAK1 MAP3K in the IL-1β signaling pathway
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DOI：
10.1016/j.bbrc.2009.02.052
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发表时间：
2009-04-10
影响因子：
3.1
通讯作者：
Takaesu, Giichi
中科院分区：
文献类型：
--
作者：
Minoda, Yasumasa;Sakurai, Hiroaki;Takaesu, Giichi
TAK1是MAP3K家族的成员，在IL-1 β和TNF α信号通路中，对JNK/p38 MAPKs和IKK的激活起着至关重要的作用。在受到刺激后，TAK1被迅速而短暂地激活。虽然TAK1在这些信号通路中的激活机制已被很好地描述，但其活性如何终止仍不清楚。为了鉴定参与TAK1调控的分子，我们对稳定表达TAP标记TAK1的HeLa细胞进行了串联亲和纯化（TAP）。FBXW5是一种F-box家族蛋白，被鉴定为IL-1 β诱导的TAK1复合体的未知成分。FBXW5以IL-1 β依赖的方式与内源性TAK1相关。FBXW5的过表达抑制IL-1 β诱导的JNK/p38 MAPKs和NF-kappa B的激活以及TAK1在Thr187上的磷酸化。相反，FBXW5的敲低导致IL-1 β刺激下TAK1的激活时间延长。这些结果表明FBXW5在IL-1 β信号通路中负调控TAK1。(C) 2009爱思唯尔公司版权所有。
TAK1, a member of the MAP3K family, plays an essential role in activation of JNK/p38 MAPKs and IKK in the IL-1 beta and TNF alpha signaling pathway. Upon stimulation, TAK1 is rapidly and transiently activated. While the activation mechanism of TAK1 in these signaling pathways is well characterized, how its activity is terminated still remains unclear. To identify the molecule(s) involved in TAK1 regulation, we performed tandem affinity purification (TAP) in HeLa cells stably expressing TAP-tagged TAK1. FBXW5, an F-box family protein, was identified as a previously unknown component of the IL-1 beta-induced TAK1 complex. FBXW5 associated with endogenous TAK1 in an IL-1 beta-dependent manner. Overexpression of FBXW5 inhibited IL-1 beta-induced activation of JNK/p38 MAPKs and NF-kappa B as well as phosphorylation of TAK1 on Thr187. Conversely, knockdown of FBXW5 resulted in the prolonged activation of TAK1 upon IL-1 beta stimulation. These results suggest that FBXW5 negatively regulates TAK1 in the IL-1 beta signaling pathway. (C) 2009 Elsevier Inc. All rights reserved.