Signal-transducing adaptor protein-2 modulates Fas-mediated T cell apoptosis by interacting with caspase-8.

Yuichi Sekine, Chikako Yamamoto, Michinori Kakisaka, Ryuta Muromoto, Shigeyuki Kon, Dai Ashitomi, Natsuko Fujita, Akihiko Yoshimura, Kenji Oritani, Tadashi Matsuda

Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.

Journal of immunology (Baltimore, Md. : 1950) 2012 Jun 15

filter terms:

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.

Citation

Yuichi Sekine, Chikako Yamamoto, Michinori Kakisaka, Ryuta Muromoto, Shigeyuki Kon, Dai Ashitomi, Natsuko Fujita, Akihiko Yoshimura, Kenji Oritani, Tadashi Matsuda. Signal-transducing adaptor protein-2 modulates Fas-mediated T cell apoptosis by interacting with caspase-8. Journal of immunology (Baltimore, Md. : 1950). 2012 Jun 15;188(12):6194-204