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

J Biol Chem. 2001 Nov 23;276(47):44069-77. doi: 10.1074/jbc.M107373200. Epub 2001 Sep 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Adaptor Proteins, Signal Transducing
  • CARD Signaling Adaptor Proteins
  • CARD8 protein, human
  • Carrier Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • Caspases

Associated data

  • GENBANK/AF405558