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pmid29177249      J+Cell+Signal 2017 ; 2 (3): ä
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  • Smyd1C Mediates CD8 T Cell Death via Regulation of Bcl2-Mediated Restriction of outer Mitochondrial Membrane Integrity #MMPMID29177249
  • Nie H; Rathbun G; Tucker H
  • J Cell Signal 2017[Sep]; 2 (3): ä PMID29177249show ga
  • The SET and Mynd domain 1 (Smyd1) locus encodes three tissue-restricted isoforms. Two previously characterized isoforms, Smyd1A and Smyd1B, are heart and skeletal muscle-restricted histone methyl transferases. Here we report that a third, non-catalytic isoform, Smyd1C, is expressed predominantly in activated CD8 T cells. While Smyd1C- deficient CD8 T cells undergo activation-induced apoptosis, neither of two classical mechanisms activation-induced cell death nor activated cell autonomous death are utilized. Instead, Smyd1C accumulates within both mitochondria and the immunological synapse where it associates with Bcl-2, FK506-Binding Protein 8/38 (FKBP38) and Calcineurin. This complex maintains Bcl-2 phosphorylation, enhanced mitochondrial localization, and restricted apoptosis of activated CD8 T cells. We suggest that CD8 T cell death is governed, in part, by Smyd1C regulation of Bcl2-mediated restriction of outer mitochondrial membrane integrity.
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