Identification of NAP1, a regulatory subunit of IκB kinase-related kinases that potentiates NF-κB signaling
Identification of NAP1, a regulatory subunit of IκB kinase-related kinases that potentiates NF-κB signaling
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DOI：
10.1128/mcb.23.21.7780-7793.2003
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发表时间：
2003-11-01
影响因子：
5.3
通讯作者：
Nakanishi, M
中科院分区：
文献类型：
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作者：
Fujita, F;Taniguchi, Y;Nakanishi, M
IkappaB激酶（IKK）相关激酶NAK（也称为TBK或T2 K）有助于激活NF-κ B依赖性基因表达。在这里，我们确定了NAP 1（NAK相关蛋白1），一种与NAK及其相关IKKi（也称为IKKi）相互作用的蛋白质。NAP 1激活NAK并促进其寡聚化。有趣的是，NAK-NAP 1复合物本身有效地磷酸化NF-κ B的p65/RelA亚基的丝氨酸536，并且这种活性被肿瘤坏死因子α（TNF-α）刺激。NAP 1的过表达特异性地增强了NF-κ B依赖性而非AP-1依赖性报告基因的细胞因子诱导。NAP 1的缺失减少了NF-κ B依赖性报告基因的表达，并使细胞对TNF-α诱导的凋亡敏感。这些结果将NAP 1定义为IKK相关激酶的激活剂，并表明NAK-NAP 1复合物可能通过促进NF-kappaB激活来保护细胞免受TNF-α诱导的细胞凋亡。
The IkappaB kinase (IKK)-related kinase NAK (also known as TBK or T2K) contributes to the activation of NF-kappaB-dependent gene expression. Here we identify NAP1 (for NAK-associated protein 1), a protein that interacts with NAK and its relative IKKepsilon (also known as IKKi). NAP1 activates NAK and facilitates its oligomerization. Interestingly, the NAK-NAP1 complex itself effectively phosphorylated serine 536 of the p65/RelA subunit of NF-kappaB, and this activity was stimulated by tumor necrosis factor alpha (TNF-alpha). Overexpression of NAP1 specifically enhanced cytokine induction of an NF-kappaB-dependent, but not an AP-1-dependent, reporter. Depletion of NAP1 reduced NF-kappaB-dependent reporter gene expression and sensitized cells to TNF-alpha-induced apoptosis. These results define NAP1 as an activator of IKK-related kinases and suggest that the NAK-NAP1 complex may protect cells from TNF-alpha-induced apoptosis by promoting NF-kappaB activation.