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Smyd1C Mediates CD8 T Cell Death via Regulation of Bcl2-Mediated Restriction of outer Mitochondrial Membrane Integrity.


ABSTRACT: 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.

SUBMITTER: Nie H 

PROVIDER: S-EPMC5699232 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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<i>Smyd1C</i> Mediates CD8 T Cell Death via Regulation of Bcl2-Mediated Restriction of outer Mitochondrial Membrane Integrity.

Nie Hui H   Rathbun Gary G   Tucker Haley H  

Journal of cell signaling 20170912 3


The SET and <i>Mynd</i> domain 1 (<i>Smyd1</i>) locus encodes three tissue-restricted isoforms. Two previously characterized isoforms, <i>Smyd1A</i> and <i>Smyd1B</i><b>,</b> are heart and skeletal muscle-restricted histone methyl transferases. Here we report that a third, non-catalytic isoform, <i>Smyd1C</i><b>,</b> is expressed predominantly in activated CD8 T cells. While <i>Smyd1C</i><b>-</b> deficient CD8 T cells undergo activation-induced apoptosis, neither of two classical mechanisms acti  ...[more]

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