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RISS 인기검색어
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- 저자 : Bettigole, Sarah E (검색결과 1 건)
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Post-translational control of T cell development by the ESCRT protein CHMP5
Adoro, Stanley,Park, Kwang Hwan,Bettigole, Sarah E,Lis, Raphael,Shin, Hee Rae,Seo, Heewon,Kim, Ju Han,Knobeloch, Klaus-Peter,Shim, Jae-Hyuck,Glimcher, Laurie H NATURE AMERICA INC 2017 NATURE IMMUNOLOGY Vol.18 No.7
<P>The acquisition of a protective vertebrate immune system hinges on the efficient generation of a diverse but self-tolerant repertoire of T cells by the thymus through mechanisms that remain incompletely resolved. Here we identified the endosomal-sorting-complex-required-for-transport (ESCRT) protein CHMP5, known to be required for the formation of multivesicular bodies, as a key sensor of thresholds for signaling via the T cell antigen receptor (TCR) that was essential for T cell development. CHMP5 enabled positive selection by promoting post-selection thymocyte survival in part through stabilization of the pro-survival protein Bcl-2. Accordingly, loss of CHMP5 in thymocyte precursor cells abolished T cell development, a phenotype that was 'rescued' by genetic deletion of the pro-apoptotic protein Bim or transgenic expression of Bcl-2. Mechanistically, positive selection resulted in the stabilization of CHMP5 by inducing its interaction with the deubiquitinase USP8. Our results thus identify CHMP5 as an essential component of the post-translational machinery required for T cell development.</P>
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