FOXO3公司
转录因子
长寿
细胞生物学
叉头转录因子
氧化应激
生物
福克斯O1
SIRT6型
细胞凋亡
乙酰化
锡尔图因
基因
遗传学
生物化学
作者
Anne Brunet,Lora B. Sweeney,James Fitzhugh Sturgill,Katrin F. Chua,Paul L. Greer,Yingxi Lin,Hien Tran,Sarah E. Ross,Raúl Mostoslavsky,Haim Y. Cohen,Linda Hu,Hwei-Ling Cheng,Mark P. Jedrychowski,Steven P. Gygi,David Sinclair,Frederick W. Alt,Michael E. Greenberg
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2004-02-24
卷期号:303 (5666): 2011-2015
被引量:3100
标识
DOI:10.1126/science.1094637
摘要
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.
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