哺乳动物的沉默信息调节因子1（SIRT1）可抑制叉头转录因子。

Mammalian SIRT1 represses forkhead transcription factors.

作者信息

Motta Maria Carla, Divecha Nullin, Lemieux Madeleine, Kamel Christopher, Chen Delin, Gu Wei, Bultsma Yvette, McBurney Michael, Guarente Leonard

机构信息

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

出版信息

Cell. 2004 Feb 20;116(4):551-63. doi: 10.1016/s0092-8674(04)00126-6.

DOI:10.1016/s0092-8674(04)00126-6

PMID:14980222

Abstract

The NAD-dependent deacetylase SIR2 and the forkhead transcription factor DAF-16 regulate lifespan in model organisms, such as yeast and C. elegans. Here we show that the mammalian SIR2 ortholog SIRT1 deacetylates and represses the activity of the forkhead transcription factor Foxo3a and other mammalian forkhead factors. This regulation appears to be in the opposite direction from the genetic interaction of SIR2 with forkhead in C. elegans. By restraining mammalian forkhead proteins, SIRT1 also reduces forkhead-dependent apoptosis. The inhibition of forkhead activity by SIRT1 parallels the effect of this deacetylase on the tumor suppressor p53. We speculate how down-regulating these two classes of damage-responsive mammalian factors may favor long lifespan under certain environmental conditions, such as calorie restriction.

摘要

NAD 依赖性去乙酰化酶 SIR2 和叉头转录因子 DAF-16 在酵母和秀丽隐杆线虫等模式生物中调节寿命。我们在此表明，哺乳动物 SIR2 的直系同源物 SIRT1 使叉头转录因子 Foxo3a 和其他哺乳动物叉头因子去乙酰化并抑制其活性。这种调节似乎与秀丽隐杆线虫中 SIR2 与叉头的遗传相互作用方向相反。通过抑制哺乳动物叉头蛋白，SIRT1 还减少了叉头依赖性凋亡。SIRT1 对叉头活性的抑制与该去乙酰化酶对肿瘤抑制因子 p53 的作用相似。我们推测，在某些环境条件下，如热量限制，下调这两类对损伤有反应的哺乳动物因子可能如何有利于长寿。