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SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction.
Aging Cell. 2007 Aug; 6(4):505-14.AC

Abstract

The sirtuin family of nicotinamide adenine dinucleotide-dependent (NAD) deacetylases plays an important role in aging and metabolic regulation. In yeast, the Sir2 gene and its homolog Hst2 independently mediate the action of caloric restriction on lifespan extension. The mammalian Sir2 ortholog, SIRT1, is up-regulated by caloric restriction and deacetylates a variety of substrates, including histones and the forkhead box O (FOXO) transcription factors. The mammalian ortholog of Hst2, SIRT2, was shown to co-localize with microtubules and functions as alpha-tubulin deacetylase. During G2/M phase, SIRT2 proteins enter nuclei and deacetylate histones. We report here that the expression of SIRT2 is elevated in the white adipose tissue and kidney of caloric-restricted mice. Oxidative stress, such as hydrogen peroxide treatment, also increases SIRT2 expression in cells. We have demonstrated that SIRT2 binds to FOXO3a and reduces its acetylation level. SIRT2 hence increases FOXO DNA binding and elevates the expression of FOXO target genes, p27(Kip1), manganese superoxide dismutase and Bim. As a consequence, SIRT2 decreases cellular levels of reactive oxygen species. Furthermore, as Bim is a pro-apoptotic factor, SIRT2 promotes cell death when cells are under severe stress. Therefore, mammalian SIRT2 responds to caloric restriction and oxidative stress to deacetylate FOXO transcription factors.

Authors+Show Affiliations

USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

17521387

Citation

Wang, Fei, et al. "SIRT2 Deacetylates FOXO3a in Response to Oxidative Stress and Caloric Restriction." Aging Cell, vol. 6, no. 4, 2007, pp. 505-14.
Wang F, Nguyen M, Qin FX, et al. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell. 2007;6(4):505-14.
Wang, F., Nguyen, M., Qin, F. X., & Tong, Q. (2007). SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell, 6(4), 505-14.
Wang F, et al. SIRT2 Deacetylates FOXO3a in Response to Oxidative Stress and Caloric Restriction. Aging Cell. 2007;6(4):505-14. PubMed PMID: 17521387.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. AU - Wang,Fei, AU - Nguyen,Margaret, AU - Qin,F Xiao-Feng, AU - Tong,Qiang, Y1 - 2007/05/23/ PY - 2007/5/25/pubmed PY - 2007/10/4/medline PY - 2007/5/25/entrez SP - 505 EP - 14 JF - Aging cell JO - Aging Cell VL - 6 IS - 4 N2 - The sirtuin family of nicotinamide adenine dinucleotide-dependent (NAD) deacetylases plays an important role in aging and metabolic regulation. In yeast, the Sir2 gene and its homolog Hst2 independently mediate the action of caloric restriction on lifespan extension. The mammalian Sir2 ortholog, SIRT1, is up-regulated by caloric restriction and deacetylates a variety of substrates, including histones and the forkhead box O (FOXO) transcription factors. The mammalian ortholog of Hst2, SIRT2, was shown to co-localize with microtubules and functions as alpha-tubulin deacetylase. During G2/M phase, SIRT2 proteins enter nuclei and deacetylate histones. We report here that the expression of SIRT2 is elevated in the white adipose tissue and kidney of caloric-restricted mice. Oxidative stress, such as hydrogen peroxide treatment, also increases SIRT2 expression in cells. We have demonstrated that SIRT2 binds to FOXO3a and reduces its acetylation level. SIRT2 hence increases FOXO DNA binding and elevates the expression of FOXO target genes, p27(Kip1), manganese superoxide dismutase and Bim. As a consequence, SIRT2 decreases cellular levels of reactive oxygen species. Furthermore, as Bim is a pro-apoptotic factor, SIRT2 promotes cell death when cells are under severe stress. Therefore, mammalian SIRT2 responds to caloric restriction and oxidative stress to deacetylate FOXO transcription factors. SN - 1474-9718 UR - https://www.unboundmedicine.com/medline/citation/17521387/SIRT2_deacetylates_FOXO3a_in_response_to_oxidative_stress_and_caloric_restriction_ L2 - https://doi.org/10.1111/j.1474-9726.2007.00304.x DB - PRIME DP - Unbound Medicine ER -