The interaction between FOXO and SIRT1: tipping the balance towards survival.
When overexpressed, the NAD-dependent protein deacetylase Sir2 extends the lifespan of both budding yeast and the nematode worm Caenorhabditis elegans. In the worm, this extension of lifespan requires the FOXO transcription factor daf-16. Three recent articles focusing on mammalian homologues of Sir2 and FOXO have highlighted the mechanisms that generate this genetic interaction. Mammalian SIRT1 deacetylates FOXO3 and/or FOXO4, thus attenuating FOXO-induced apoptosis and potentiating FOXO-induced cell-cycle arrest. SIRT1 might increase longevity by shifting FOXO dependent responses away from cell death and towards cell survival.
Giannakou
Maria E
ME
Department of Biology, University College London, London WC1E 6BT, UK.
Partridge
Linda
L
D000818:Animals; D018797:Cell Cycle Proteins; D002470:Cell Survival / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; C108803:FOXO4 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D014157:Transcription Factors; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D006655:Histone Deacetylases