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 a...

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Bibliographic Details
Published inMolecular and cellular biology Vol. 23; no. 21; p. 7780
Main Authors Fujita, Fumitaka, Taniguchi, Yuko, Kato, Takashi, Narita, Yasuko, Furuya, Akiko, Ogawa, Tatsuhiro, Sakurai, Hiroaki, Joh, Takashi, Itoh, Makoto, Delhase, Mireille, Karin, Michael, Nakanishi, Makoto
Format Journal Article
LanguageEnglish
Published United States 01.11.2003
Subjects
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Amino Acid Sequence
Animals
Enzyme Activation
Genes, Reporter
HeLa Cells
Humans
I-kappa B Kinase
Mice
Molecular Sequence Data
NF-kappa B - metabolism
Protein Binding
Protein Subunits - genetics
Protein Subunits - metabolism
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
RNA, Small Interfering - metabolism
Sequence Alignment
Signal Transduction - physiology
Tissue Distribution
Tumor Necrosis Factor-alpha - metabolism
Two-Hybrid System Techniques
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Summary: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.
ISSN:0270-7306
1098-5549