Biochem Biophys Res Commun. 2003 Mar 28;303(1):69-73.

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

Masumoto, J., Dowds, T. A., Schaner, P., Chen, F. F., Ogura, Y., Li, M., Zhu, L., Katsuyama, T., Sagara, J., Taniguchi, S., Gumucio, D. L., Nunez, G., Inohara, N.,
--- - Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
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.
PMID: 12646168External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD ASC Link CARD12 Co-immunoprecipitation HEK293 Not specified Full length Not specified 1-647 12646168
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
CARD ASC Link CARD12 β-galactosidase staining, Luciferase assay Apoptosis NF-kB activation 12646168
(Link: click this icon to show interactions only between the two corresponding DDs)