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

• Published in: Biochemical and biophysical research communications Vol. 303; no. 1; pp. 69 - 73
• Main Authors: Masumoto, Junya, Dowds, Theresa A, Schaner, Philip, Chen, Felicia F, Ogura, Yasunori, Li, Mu, Zhu, Li, Katsuyama, Tsutomu, Sagara, Junji, Taniguchi, Shun'ichiro, Gumucio, Deborah L, Núñez, Gabriel, Inohara, Naohiro
• Format: Journal Article
• Language: English
• Published: United States 28-03-2003
• Subjects: Animals; Apoptosis; Apoptosis Regulatory Proteins; 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
• ISSN: 0006-291X
• 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.