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

Wen Hui Hu, Xian Ming Mo, Winston M. Walters, Roberta Brambilla, John R Bethea

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

NF-κB-inducing kinase (NIK) has been implicated as an essential component of NF-κB 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-κB activation induced by tumor necrosis factor (TNF)-α, TNF receptor 1, TRADD, RIP, TRAF2, and NIK but does not affect IKK1- and IKK2-mediated NF-κB activation. Knockdown of TNAP by lentiviral-mediated small interference RNA potentiates TNF-α-induced NF-κB 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-κB signaling pathways.

Original languageEnglish (US)
Pages (from-to)35975-35983
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number34
DOIs
StatePublished - Aug 20 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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