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An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways.

Nod1 is an Apaf-1-like molecule composed of a caspase-recruitment domain (CARD), nucleotide-binding domain, and leucine-rich repeats that associates with the CARD-containing kinase RICK and activates nuclear factor kappaB (NF-kappaB). We show that self-association of Nod1 mediates proximity of RICK and the interaction of RICK with the gamma subunit of the IkappaB kinase (IKKgamma). Similarly, the RICK-related kinase RIP associated via its intermediate region with IKKgamma. A mutant form of IKKgamma deficient in binding to IKKalpha and IKKbeta inhibited NF-kappaB activation induced by RICK or RIP. Enforced oligomerization of RICK or RIP as well as of IKKgamma, IKKalpha, or IKKbeta was sufficient for induction of NF-kappaB activation. Thus, the proximity of RICK, RIP, and IKK complexes may play an important role for NF-kappaB activation during Nod1 oligomerization or trimerization of the tumor necrosis factor alpha receptor.

Pubmed ID: 10880512


  • Inohara N
  • Koseki T
  • Lin J
  • del Peso L
  • Lucas PC
  • Chen FF
  • Ogura Y
  • Núñez G


The Journal of biological chemistry

Publication Data

September 8, 2000

Associated Grants

  • Agency: NCI NIH HHS, Id: CA-64556

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Apoptosis
  • Carrier Proteins
  • Cell Line
  • Fibroblasts
  • Humans
  • I-kappa B Kinase
  • Mice
  • NF-kappa B
  • Nod1 Signaling Adaptor Protein
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Proteins
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Sequence Deletion
  • Signal Transduction
  • Transcription, Genetic
  • Transfection