The α and β subunits of IκB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF
The α and β subunits of IκB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF
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DOI：
10.1128/mcb.21.12.3986-3994.2001
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发表时间：
2001-06-01
影响因子：
5.3
通讯作者：
Liu, ZG
中科院分区：
文献类型：
--
作者：
Devin, A;Lin, Y;Liu, ZG
I κ b激酶（IKK）的激活是转录因子nf - κ b核易位的关键步骤。IKK是由三个亚基组成的复合物：IKK α， IKK β和IKK γ（也称为NEMO）。在对促炎细胞因子肿瘤坏死因子（TNF）的反应中，IKK通过TNF受体相关因子2 （TRAF2）被募集到TNF受体1 （TNF- r1）复合体后被激活。我们发现IKK α和IKK β催化亚基是IKK- traf2相互作用所必需的。这种相互作用通过IKK α、IKK β和TRAF2的环指结构域共有的亮氨酸拉链基序发生，仅IKKa或IKK β就足以使IKK募集到TNF-R1。重要的是，IKK γ对于tnf诱导的IKK募集到TNF-R1并不是必需的，因为这在IKK γ缺乏的细胞中有效发生。使用TRAF2（-/-）细胞，我们证明了tnf诱导的IKK γ和死亡结构域激酶RIP之间的相互作用依赖于TRAF2，这种相互作用的一个可能功能是在IKK复合物与TRAF2相互作用时稳定IKK复合物。
The activation of I kappaB kinase (IKK) is a key step in the nuclear translocation of the transcription factor NF-kappaB. IKK is a complex composed of three subunits: IKK alpha, IKK beta, and IKK gamma (also called NEMO). In response to the proinflammatory cytokine tumor necrosis factor (TNF), IKK is activated after being recruited to the TNF receptor 1 (TNF-R1) complex via TNF receptor-associated factor 2 (TRAF2). We found that the IKK alpha and IKK beta catalytic subunits are required for IKK-TRAF2 interaction. This interaction occurs through the leucine zipper motif common to IKK alpha, IKK beta, and the RING finger domain of TRAF2, and either IKKa or IKK beta alone is sufficient for the recruitment of IKK to TNF-R1. Importantly, IKK gamma is not essential for TNF-induced IKK recruitment to TNF-R1, as this occurs efficiently in IKK gamma -deficient cells. Using TRAF2(-/-) cells, we demonstrated that the TNF-induced interaction between IKK gamma and the death domain kinase RIP is TRAF2 dependent and that one possible function of this interaction is to stabilize the IKK complex when it interacts with TRAF2.