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

@article{citeulike:2333111, 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.}, address = {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.}, author = {Brunet, A. and Sweeney, L. B. and Sturgill, J. F. and Chua, K. F. and Greer, P. L. and Lin, Y. and Tran, H. and Ross, S. E. and Mostoslavsky, R. and Cohen, H. Y. and Hu, L. S. and Cheng, H. L. and Jedrychowski, M. P. and Gygi, S. P. and Sinclair, D. A. and Alt, F. W. and Greenberg, M. E. }, citeulike-article-id = {2333111}, doi = {http://dx.doi.org/10.1126/science.1094637}, issn = {1095-9203}, journal = {Science}, keywords = {foxo, sirt1, sirtuin}, month = {March}, number = {5666}, pages = {2011--2015}, posted-at = {2008-04-02 04:24:47}, priority = {2}, title = {Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase.}, url = {http://dx.doi.org/10.1126/science.1094637}, volume = {303}, year = {2004} }

TY - JOUR ID - citeulike:2333111 L3 - citeulike-article-id:2333111 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. IS - 5666 JF - Science SN - 1095-9203 AD - 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. EP - 2015 TI - Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. VL - 303 SP - 2011 KW - foxo KW - sirt1 KW - sirtuin AU - Brunet, A AU - Sweeney, LB AU - Sturgill, JF AU - Chua, KF AU - Greer, PL AU - Lin, Y AU - Tran, H AU - Ross, SE AU - Mostoslavsky, R AU - Cohen, HY AU - Hu, LS AU - Cheng, HL AU - Jedrychowski, MP AU - Gygi, SP AU - Sinclair, DA AU - Alt, FW AU - Greenberg, ME PY - 2004/03/26/ UR - http://dx.doi.org/10.1126/science.1094637 ER -