Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling.

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 IKK epsilon (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.
Mesh Terms:
Amino Acid Sequence, Animals, Enzyme Activation, Genes, Reporter, HeLa Cells, Humans, I-kappa B Kinase, Mice, Molecular Sequence Data, NF-kappa B, Protein Binding, Protein Subunits, Protein-Serine-Threonine Kinases, RNA, Small Interfering, Recombinant Fusion Proteins, Sequence Alignment, Signal Transduction, Tissue Distribution, Tumor Necrosis Factor-alpha, Two-Hybrid System Techniques
Mol. Cell. Biol.
Date: Nov. 01, 2003
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