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

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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.

Original languageEnglish
Pages (from-to)6194-6204
Number of pages11
JournalJournal of Immunology
Volume188
Issue number12
DOIs
Publication statusPublished - 2012 Jun 15

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ASJC Scopus subject areas

  • Immunology

Cite this

Sekine, Y., Yamamoto, C., Kakisaka, M., Muromoto, R., Kon, S., Ashitomi, D., Fujita, N., Yoshimura, A., Oritani, K., & Matsuda, T. (2012). Signal-transducing adaptor protein-2 modulates fas-mediated T cell apoptosis by interacting with caspase-8. Journal of Immunology, 188(12), 6194-6204. https://doi.org/10.4049/jimmunol.1103467