Molecular Cloning and Characterization of NAKBP, which bind to a novel IKK-Kinase, NAK

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The IκB kinase (IKK)-related kinase NAK (also known as TBK or T2K) contributes to the activation of NF-κB-dependent gene expression. Here we identify NAP1 (for NAK-associated protein 1), a protein that interacts with NAK and its relative IKKε(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-κB, and this activity was stimulated by tumor necrosis factor alpha (TNF-α).Overexpression of NAP1 specifically enhanced cytokine induction of an NF-κB-dependent reporter gene expression and sensitized cells to TNF-α-induced apoptosis. These results define NAP1 as an activator of IKKK-related kinases and suggest that the NAK-NAP1 complex may protect cells from TNF-α-induced apoptosis by promoting NF-κB activation.