Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase

A. Brunet, L.B.J. Sweeney, J.F. Sturgill, K. Chua, P. Greer, Y. Lin, H. Tran, S. Ross, R. Mostoslavsky, H. Cohen, L. Hu, H.-L. Chen, M. Jedrychowski, S. Gygi, D. Sinclair, F. Alt, M. Greenberg, Science 303 (2004) 2011–2015.

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Journal Article | Published | English
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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.
Publishing Year
Date Published
2004-03-26
Journal Title
Science
Volume
303
Issue
5666
Page
2011-2015
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Brunet A, Sweeney LBJ, Sturgill JF, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004;303(5666):2011-2015. doi:10.1126/science.1094637
Brunet, A., Sweeney, L. B. J., Sturgill, J. F., Chua, K., Greer, P., Lin, Y., … Greenberg, M. (2004). Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science, 303(5666), 2011–2015. https://doi.org/10.1126/science.1094637
Brunet, Anne, Lora Beatrice Jaeger Sweeney, J Fitzhugh Sturgill, Katrin Chua, Paul Greer, Yingxi Lin, Hien Tran, et al. “Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase.” Science 303, no. 5666 (2004): 2011–15. https://doi.org/10.1126/science.1094637.
A. Brunet et al., “Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase,” Science, vol. 303, no. 5666, pp. 2011–2015, 2004.
Brunet A, Sweeney LBJ, Sturgill JF, Chua K, Greer P, Lin Y, Tran H, Ross S, Mostoslavsky R, Cohen H, Hu L, Chen H-L, Jedrychowski M, Gygi S, Sinclair D, Alt F, Greenberg M. 2004. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 303(5666), 2011–2015.
Brunet, Anne, et al. “Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase.” Science, vol. 303, no. 5666, American Association for the Advancement of Science, 2004, pp. 2011–15, doi:10.1126/science.1094637.

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