Caspase-mediated changes in Sir2α during apoptosis

Silent information regulator 2 (Sir2) is an NAD+-dependent histone deacetylase that establishes repressive chromatin status and extends the life span of both budding yeast and the nematode worm Caenorhabditis elegans. There is growing evidence that its mammalian homologue Sir2α protects cells from stress-induced apoptosis. We report here that mammalian Sir2α was directly cleaved by both initiator and executioner caspases, and relocated from the nucleus to the cytoplasm in apoptotic cells. These alterations of Sir2α were largely inhibited by a caspase-9 dominant-negative mutant or Bcl-xL. Our results indicate that Sir2α undergoes dynamic changes in caspase-dependent manner during apoptosis.