Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-κB

Naohiro Inohara, Takeyoshi Koseki, Luis Del Peso, Yuanming Hu, Christina Yee, Shu Chen, Roberto Carrio, Jesus Merino, Ding Liu, Jian Ni, Gabriel Núñez

Research output: Contribution to journalArticle

578 Citations (Scopus)

Abstract

Ced-4 and Apaf-1 belong to a major class of apoptosis regulators that contain caspase-recruitment (CARD) and nucleotide-binding oligomerization domains. Nod1, a protein with an NH2-terminal CARD-linked to a nucleotide- binding domain and a COOH-terminal segment with multiple leucine-rich repeats, was identified. Nod-1 was found to bind to multiple caspases with long prodomains, but specifically activated caspase-9 and promoted caspase- 9-induced apoptosis. As reported for Apaf-1, Nod1 required both the CARD and P-loop for function. Unlike Apaf-1, Nod1 induced activation of nuclear factor-kappa-B (NF-κB) and bound RICK, a CARD-containing kinase that also induces NF-κB activation. Nod1 mutants inhibited NF-κB activity induced by RICK, but not that resulting from tumor necrosis factor-α stimulation. Thus, Nod1 is a leucine-rich repeat-containing Apaf-1-like molecule that can regulate both apoptosis and NF-κB activation pathways.

Original languageEnglish
Pages (from-to)14560-14567
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number21
DOIs
Publication statusPublished - 1999 May 21
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Inohara, N., Koseki, T., Del Peso, L., Hu, Y., Yee, C., Chen, S., Carrio, R., Merino, J., Liu, D., Ni, J., & Núñez, G. (1999). Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-κB. Journal of Biological Chemistry, 274(21), 14560-14567. https://doi.org/10.1074/jbc.274.21.14560