Caspase-mediated changes in Sir2alpha 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 Sir2alpha protects cells from stress-induced apoptosis. We report here that mammalian Sir2alpha was directly cleaved by both initiator and executioner caspases, and relocated from the nucleus to the cytoplasm in apoptotic cells. These alterations of Sir2alpha were largely inhibited by a caspase-9 dominant-negative mutant or Bcl-xL. Our results indicate that Sir2alpha undergoes dynamic changes in caspase-dependent manner during apoptosis.
Ohsawa
Shizue
S
Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Miura
Masayuki
M
D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D061945:Caspase Inhibitors; D011994:Recombinant Proteins; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins