ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis

Biochem Biophys Res Commun. 2003 Mar 28;303(1):69-73. doi: 10.1016/s0006-291x(03)00309-7.


ASC is a pro-apoptotic protein containing a pyrin domain (PD) and a caspase-recruitment domain (CARD). A previous study suggests that ASC interacts with Ipaf, a member of the Apaf-1/Nod1 protein family. However, the functional relevance of the interaction has not been determined. Here, we report that co-expression of ASC with Ipaf or oligomerization of ASC induces both apoptosis and NF-kappa B activation. Apoptosis induced through ASC was inhibited by a mutant form of Caspase-8 but not by that of Caspase-1. The PD of ASC physically interacted with Caspase-8 as well as with pyrin, the familial Mediterranean fever gene product. Caspase-8 deficiency rescued mouse fibroblasts from apoptosis induced by ASC oligomerization. Pyrin disrupted the interaction between ASC and Caspase-8, and inhibited both apoptosis and NF-kappa B activation induced by ASC. These findings suggest that ASC is a mediator of NF-kappa B activation and Caspase-8-dependent apoptosis in an Ipaf signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • CARD Signaling Adaptor Proteins
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism*
  • Cell Death
  • Cell Line
  • Cytoskeletal Proteins / metabolism*
  • Cytoskeletal Proteins / physiology*
  • Enzyme Activation
  • Fibroblasts / metabolism
  • Humans
  • Mice
  • NF-kappa B / metabolism*
  • Plasmids / metabolism
  • Precipitin Tests
  • Protein Binding
  • Proteins / metabolism
  • Pyrin
  • Signal Transduction
  • Transfection


  • Apoptosis Regulatory Proteins
  • CARD Signaling Adaptor Proteins
  • Cytoskeletal Proteins
  • MEFV protein, human
  • Mefv protein, mouse
  • NF-kappa B
  • PYCARD protein, human
  • Proteins
  • Pycard protein, mouse
  • Pyrin
  • CASP8 protein, human
  • CASP9 protein, human
  • Casp8 protein, mouse
  • Casp9 protein, mouse
  • Caspase 8
  • Caspase 9
  • Caspases