CARDINAL, a novel caspase recruitment domain protein, is an inhibitor of multiple NF-kappa B activation pathways

L Bouchier-Hayes, H Conroy, H Egan, C Adrain, E M Creagh, M MacFarlane, S J Martin

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Proteins possessing the caspase recruitment domain (CARD) motif have been implicated in pathways leading to activation of caspases or NF-kappaB in the context of apoptosis or inflammation, respectively. Here we report the identification of a novel protein, CARDINAL, that contains a CARD motif and also exhibits a high degree of homology to the C terminus of DEFCAP/NAC, a recently described member of the Apaf-1/Nod-1 family. In contrast with the majority of CARD proteins described to date, CARDINAL failed to promote apoptosis or NF-kappaB activation. Rather, CARDINAL potently suppressed NF-kappaB activation associated with overexpression of TRAIL-R1, TRAIL-R2, RIP, RICK, Bcl10, and TRADD, or through ligand-induced stimulation of the interleukin-1 or tumor necrosis factor receptors. Co-immunoprecipitation experiments revealed that CARDINAL interacts with the regulatory subunit of the IkappaB kinase (IKK) complex, IKKgamma (NEMO), providing a molecular basis for CARDINAL function. Thus, CARDINAL is a novel regulator of NF-kappaB activation in the context of pro-inflammatory signals.

Original languageEnglish
Pages (from-to)44069-77
Number of pages9
JournalThe Journal of biological chemistry
Volume276
Issue number47
DOIs
Publication statusPublished - 23 Nov 2001

Keywords

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • CARD Signaling Adaptor Proteins
  • Carrier Proteins/chemistry
  • Caspases/metabolism
  • Cell Line
  • Humans
  • Molecular Sequence Data
  • NF-kappa B/chemistry
  • Neoplasm Proteins
  • Precipitin Tests
  • Sequence Homology, Amino Acid
  • Subcellular Fractions/metabolism

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