Control of canonical NF-κB activation through the NIK-IKK complex pathway
Control of canonical NF-κB activation through the NIK-IKK complex pathway
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DOI：
10.1073/pnas.0707959105
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发表时间：
2008-03-04
影响因子：
11.1
通讯作者：
Cheng, Genhong
中科院分区：
文献类型：
--
作者：
Zarnegar, Brian;Yamazaki, Soh;Cheng, Genhong
近年来的文章描述了两种不同的不同的核因子-kappa B激活途径，它们导致含有p50或p52的核因子-kappa B复合体的不同激活。检测肿瘤坏死因子受体相关因子(TRAF)的研究已经证实，TRAF2、TRAF5和TRAF6，而不是TRAF3，在规范的(p50依赖的)NF-kappa B激活中起积极作用。相反，最近报道TRAF3在非规范(p52依赖)的NF-kappa B途径中起着重要的负调节作用。在这篇文章中，我们提供了TRAF3在体外和体内有效地抑制典型的核因子-kappaB的激活和基因表达的证据。我们还证明，TRAF3缺陷细胞中典型的NF-kappa B途径的解除调控是由于NF-kappa B诱导激酶(NIK)的积聚，NIK是介导非典型的NF-kappa B激活的基本激酶。因此，我们的数据表明，抑制TRAF3导致两个NF-kappa B激活通路的协调激活。
Articles in recent years have described two separate and distinct NF-kappa B activation pathways that result in the differential activation of p50- or p52-containing NF-kappa B complexes. Studies examining tumor-necrosis factor receptor-associated factors (TRAFs) have identified positive roles for TRAF2, TRAF5, and TRAF6, but not TRAF3, in canonical (p50-dependent) NF-kappa B activation. Conversely, it recently was reported that TRAF3 functions as an essential negative regulator of the noncanonical (p52-dependent) NF-kappa B pathway. In this article, we provide evidence that TRAF3 potently suppresses canonical NF-kappa B activation and gene expression in vitro and in vivo. We also demonstrate that deregulation of the canonical NF-kappa B pathway in TRAF3-deficient cells results from accumulation of NF-kappa B-inducing kinase (NIK), the essential kinase mediating noncanonical NF-kappa B activation. Thus, our data demonstrate that inhibition of TRAF3 results in coordinated activation of both NF-kappa B activation pathways.