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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.

Pubmed ID: 14560022


  • Fujita F
  • Taniguchi Y
  • Kato T
  • Narita Y
  • Furuya A
  • Ogawa T
  • Sakurai H
  • Joh T
  • Itoh M
  • Delhase M
  • Karin M
  • Nakanishi M


Molecular and cellular biology

Publication Data

November 15, 2003

Associated Grants


Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • 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