The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation
The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation
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DOI：
10.1016/s1074-7613(00)80194-6
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发表时间：
2000-04-01
期刊：
影响因子：
32.4
通讯作者：
Liu, ZG
中科院分区：
文献类型：
--
作者：
Devin, A;Cook, A;Liu, ZG
死亡结构域激酶RIP和TNF受体相关因子2（TRAF 2）是TNF信号传导中的重要效应物。为了了解RIP和TRAF 2调节TNF诱导的转录因子NF-κ B激活的机制，我们使用RIP-/-和TRAF 2（-/-）成纤维细胞研究了它们在TNF-R1介导的IKK激活中各自的作用。我们发现TNF-R1介导的IKK激活需要RIP和TRAF 2蛋白。尽管TRAF 2或RIP可以独立地募集到TNF-R1复合物中，但它们中的任何一个都不能单独转导导致IKK激活的TNF信号。此外，我们证明了IKK在TNF治疗后通过TRAF 2被募集到TNF-R1复合物中，并且IKK的激活需要RIP在同一复合物中的存在。
The death domain kinase RIP and the TNF receptor-associated factor 2 (TRAF2) are essential effecters in TNF signaling. To understand the mechanism by which RIP and TRAF2 regulate TNF-induced activation of the transcription factor NF-KB, we investigated their respective roles in TNF-R1-mediated IKK activation using both RIP-/- and TRAF2(-/-) fibroblasts. We found that TNF-R1-mediated IKK activation requires both RIP and TRAF2 proteins. Although TRAF2 or RIP can be independently recruited to the TNF-R1 complex, neither one of them alone is capable of transducing the TNF signal that leads to IKK activation. Moreover, we demonstrated that IKK is recruited to the TNF-R1 complex through TRAF2 upon TNF treatment and that IKK activation requires the presence of RIP in the same complex.