Meta-Biol

• Pathways

SIRT1, an NAD-dependent histone deacetylase, deacetylates FOXO3. SIRT1-mediated deacetylation of FOXO3 inhibits FOXO3-mediated cell death induced by oxidative stress while promoting FOXO3-mediated cell cycle arrest, which increases resistance to oxidative stress (Brunet et al. 2004).
FOXO3 can similarly be deacetylated by SIRT3, also an NAD-dependent histone deacetylase. Deacetylation of FOXO3 by SIRT3 in response to oxidative stress increases FOXO3 nuclear localization by interfering with AKT-mediated phosphorylation of FOXO3. SIRT3-mediated deacetylation of FOXO3 positively regulates FOXO3-mediated transcription of SOD2 and CAT genes which encode enzymes that process reactive oxygen species and reduce oxidative stress to the cell (Kim et al. 2010, Tseng et al. 2013).