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

Naohiro Inohara, Takeyoshi Koseki, Jingmei Lin, Luis Del Peso, Peter C. Lucas, Felicia F. Chen, Yasunori Ogura, Gabriel Núñez

Research output: Contribution to journalArticlepeer-review

426 Scopus citations

Abstract

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 κB (NF-κB). We show that self-association of Nod1 mediates proximity of RICK and the interaction of RICK with the γ subunit of the IκB kinase (IKKγ). Similarly, the RICK-related kinase RIP associated via its intermediate region with IKKγ. A mutant form of IKKγ deficient in binding to IKKα and IKKβ inhibited NF-κB activation induced by RICK or RIP. Enforced oligomerization of RICK or RIP as well as of IKKγ, IKKα, or IKKβ was sufficient for induction of NF-κB activation. Thus, the proximity of RICK, RIP, and IKK complexes may play an important role for NF-κB activation during Nod1 oligomerization or trimerization of the tumor necrosis factor α receptor.

Original languageEnglish (US)
Pages (from-to)27823-27831
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number36
DOIs
StatePublished - Sep 8 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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