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CARD6 is a modulator of NF-kappa B activation by Nod1- and Cardiak-mediated pathways

Christian Stehlik1, Hideki Hayashi, Frederick Pio

  • 1Burnham Institute, La Jolla, California 92037, USA.

The Journal of Biological Chemistry
|May 31, 2003
PubMed

Insights

We identified a new protein, CARD6, that selectively regulates inflammatory pathways. CARD6 interacts with specific CARD-family proteins, modulating NF-kappa B activation, but not other immune responses like caspase-1 or apoptosis.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Caspase recruitment domain (CARD)-containing proteins are crucial in inflammatory signaling pathways, including NF-kappa B and caspase-1 activation.
  • Understanding the intricate interactions within the CARD protein family is essential for deciphering innate immunity mechanisms.

Purpose of the Study:

  • To clone and characterize a novel CARD protein, CARD6, and investigate its interactions and functional role in cellular signaling pathways.
  • To determine the specificity of CARD6 interactions with other CARD-family members and its impact on NF-kappa B and caspase-1 activation.

Main Methods:

  • Cloning of a novel CARD6 cDNA.
  • Immunoprecipitation assays to detect protein-protein interactions.
  • Transfection experiments to assess functional effects on NF-kappa B and caspase-1 activation.

Main Results:

  • CARD6 specifically binds to Nod1, Cardiak, NAC, and TUCAN, but not other CARD proteins.
  • Cardiak and Nod1 influence CARD6 phosphorylation and expression, suggesting functional interplay.
  • CARD6 selectively suppresses NF-kappa B induction by Nod1 and Cardiak, without affecting pathways mediated by Bcl10 or TNF-alpha.
  • CARD6 does not inhibit caspase-1-dependent IL-1 beta secretion or apoptosis induced by other stimuli.

Conclusions:

  • CARD6 is a novel, selective modulator of NF-kappa B activation, specifically targeting Nod1 and Cardiak-dependent inflammatory pathways.
  • This finding expands the repertoire of CARD-family proteins involved in regulating innate immunity and inflammatory responses.

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