SIRT1,SIRT3 deacetylate FOXO3

Stable Identifier
Reaction [transition]
Homo sapiens
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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).
Literature References
PubMed ID Title Journal Year
14976264 Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase

Sinclair, DA, Jedrychowski, MP, Greenberg, ME, Brunet, A, Alt, FW, Gygi, SP, Hu, LS, Ross, SE, Lin, Y, Cohen, HY, Sweeney, LB, Chua, KF, Sturgill, JF, Mostoslavsky, R, Tran, H, Cheng, HL, Greer, PL

Science 2004
23665396 SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage

Tseng, AH, Shieh, SS, Wang, DL

Free Radic. Biol. Med. 2013
Catalyst Activity

NAD-dependent protein deacetylase activity of SIRT1,SIRT3 [nucleoplasm]

Orthologous Events
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