title: ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis.
abstract: 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.
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Junya
authors.initials: J
authors.lastname: Masumoto
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Dowds
authors.forename: Philip
authors.initials: P
authors.lastname: Schaner
authors.forename: Felicia F
authors.initials: FF
authors.lastname: Chen
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ogura
authors.forename: Mu
authors.initials: M
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Katsuyama
authors.forename: Junji
authors.initials: J
authors.lastname: Sagara
authors.forename: Shun'ichiro
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Gumucio
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
authors.forename: Naohiro
authors.initials: N
authors.lastname: Inohara
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism* / Q000502:physiology*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D000071198:Pyrin; D015398:Signal Transduction; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; C000604193:Mefv protein, mouse; D016328:NF-kappa B; C402202:PYCARD protein, human; D011506:Proteins; C498534:Pycard protein, mouse; D000071198:Pyrin; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases