TNAP, a novel repressor of NF-kappaB-inducing kinase, suppresses NF-kappaB activation.
NF-kappaB-inducing kinase (NIK) has been implicated as an essential component of NF-kappaB 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 ... or IKK2. TNAP specifically inhibits NF-kappaB 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-kappaB activation. Knockdown of TNAP by lentiviral-mediated small interference RNA potentiates TNF-alpha-induced NF-kappaB activation. TNAP suppresses NIK kinase activity and subsequently reduces p100 processing, p65 phosphorylation, and IkappaBalpha degradation. These data suggest that TNAP is a repressor of NIK activity and regulates both the classical and alternative NF-kappaB signaling pathways.
Mesh Terms:
Carrier Proteins, Cloning, Molecular, Enzyme Activation, Humans, NF-kappa B, Protein-Serine-Threonine Kinases, Repressor Proteins, Signal Transduction, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Carrier Proteins, Cloning, Molecular, Enzyme Activation, Humans, NF-kappa B, Protein-Serine-Threonine Kinases, Repressor Proteins, Signal Transduction, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
J. Biol. Chem.
Date: Aug. 20, 2004
PubMed ID: 15208311
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