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TNAP, a novel repressor of NF-kappaB-inducing kinase, suppresses NF-kappaB activation

Item Type:Article
Title:TNAP, a novel repressor of NF-kappaB-inducing kinase, suppresses NF-kappaB activation
Creators Name:Hu, W.H. and Mo, X.M. and Walters, W.M. and Brambilla, R. and Bethea, J.R.
Abstract:NF-{kappa}B-inducing kinase (NIK) has been implicated as an essential component of NF-{kappa}B activation. However, the regulatory mechanism of NIK signaling remains elusive. We have identified a novel NIK interacting protein, TNAP (for TRAFs and NIK-associated protein). In mammalian cells, TNAP physically interacts with NIK, TRAF2, and TRAF3 but not IKK1 of IKK2. TNAP specifically inhibits NF-{kappa}B activation induced by tumor necrosis factor (TNF)-{alpha}, TNF receptor 1, TRADD, RIP, TRAF2, and NIK but does not affect IKK1- and IKK2-mediated NF-{kappa}B activation. Knockdown of TNAP by lentiviral-mediated small interference RNA potentiates TNF-{alpha}-induced NF-{kappa}B activation. TNAP suppresses NIK kinase activity and subsequently reduces p100 processing, p65 phosphorylation, and IκBα degradation. These data suggest that TNAP is a repressor of NIK activity and regulates both the classical and alternative NF-{kappa}B signaling pathways.
Keywords:Carrier Proteins, Enzyme Activation, Molecular Cloning, NF-Kappa B, Protein-Serine-Threonine Kinases, Proteins, Repressor Proteins, Signal Transduction, Tumor Necrosis Factor Receptor-Associated Peptides and
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:279
Number:34
Page Range:35975-35983
Date:1 January 2004
Official Publication:https://doi.org/10.1074/jbc.M405699200
PubMed:View item in PubMed

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