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Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase.
Science. 2004 Mar 26; 303(5666):2011-5.Sci

Abstract

The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.

Authors+Show Affiliations

Division of Neuroscience, Children's Hospital, and Department of Neurobiology, Center for Blood Research (CBR) Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

14976264

Citation

Brunet, Anne, et al. "Stress-dependent Regulation of FOXO Transcription Factors By the SIRT1 Deacetylase." Science (New York, N.Y.), vol. 303, no. 5666, 2004, pp. 2011-5.
Brunet A, Sweeney LB, Sturgill JF, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004;303(5666):2011-5.
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., Hu, L. S., Cheng, H. L., Jedrychowski, M. P., Gygi, S. P., Sinclair, D. A., Alt, F. W., & Greenberg, M. E. (2004). Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science (New York, N.Y.), 303(5666), 2011-5.
Brunet A, et al. Stress-dependent Regulation of FOXO Transcription Factors By the SIRT1 Deacetylase. Science. 2004 Mar 26;303(5666):2011-5. PubMed PMID: 14976264.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. AU - Brunet,Anne, AU - Sweeney,Lora B, AU - Sturgill,J Fitzhugh, AU - Chua,Katrin F, AU - Greer,Paul L, AU - Lin,Yingxi, AU - Tran,Hien, AU - Ross,Sarah E, AU - Mostoslavsky,Raul, AU - Cohen,Haim Y, AU - Hu,Linda S, AU - Cheng,Hwei-Ling, AU - Jedrychowski,Mark P, AU - Gygi,Steven P, AU - Sinclair,David A, AU - Alt,Frederick W, AU - Greenberg,Michael E, Y1 - 2004/02/19/ PY - 2004/2/21/pubmed PY - 2004/4/23/medline PY - 2004/2/21/entrez SP - 2011 EP - 5 JF - Science (New York, N.Y.) JO - Science VL - 303 IS - 5666 N2 - The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/14976264/Stress_dependent_regulation_of_FOXO_transcription_factors_by_the_SIRT1_deacetylase_ L2 - http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=14976264 DB - PRIME DP - Unbound Medicine ER -