title: Signal-transducing adaptor protein-2 modulates Fas-mediated T cell apoptosis by interacting with caspase-8.
abstract: We found that an adaptor protein, signal-transducing adaptor protein (STAP)-2, is a new member of the Fas-death-inducing signaling complex and participates in activation-induced cell death in T cells. STAP-2 enhanced Fas-mediated apoptosis and caspase-8 aggregation and activation in Jurkat T cells. Importantly, STAP-2 directly interacted with caspase-8 and Fas, resulting in enhanced interactions between caspase-8 and FADD in the Fas-death-inducing signaling complex. Moreover, STAP-2 protein has a consensus caspase-8 cleavage sequence, VEAD, in its C-terminal domain, and processing of STAP-2 by caspase-8 was crucial for Fas-induced apoptosis. Physiologic roles of STAP-2 were confirmed by observations that STAP-2-deficient mice displayed impaired activation-induced cell death and superantigen-induced T cell depletion. Therefore, STAP-2 is a novel participant in the regulation of T cell apoptosis after stimulation.
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sekine
authors.forename: Chikako
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Michinori
authors.initials: M
authors.lastname: Kakisaka
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.forename: Dai
authors.initials: D
authors.lastname: Ashitomi
authors.forename: Natsuko
authors.initials: N
authors.lastname: Fujita
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015153:Blotting, Western; D053181:Caspase 8 / Q000276:immunology / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053200:Fas-Associated Death Domain Protein; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C413897:STAP2 protein, human; C523144:STAP2 protein, mouse; D019014:fas Receptor; D053181:Caspase 8