FOXO与SIRT1之间的相互作用：向生存倾斜平衡。

The interaction between FOXO and SIRT1: tipping the balance towards survival.

作者信息

Giannakou Maria E, Partridge Linda

机构信息

Department of Biology, University College London, London WC1E 6BT, UK.

出版信息

Trends Cell Biol. 2004 Aug;14(8):408-12. doi: 10.1016/j.tcb.2004.07.006.

DOI:10.1016/j.tcb.2004.07.006

PMID:15308206

Abstract

When overexpressed, the NAD-dependent protein deacetylase Sir2 extends the lifespan of both budding yeast and the nematode worm Caenorhabditis elegans. In the worm, this extension of lifespan requires the FOXO transcription factor daf-16. Three recent articles focusing on mammalian homologues of Sir2 and FOXO have highlighted the mechanisms that generate this genetic interaction. Mammalian SIRT1 deacetylates FOXO3 and/or FOXO4, thus attenuating FOXO-induced apoptosis and potentiating FOXO-induced cell-cycle arrest. SIRT1 might increase longevity by shifting FOXO dependent responses away from cell death and towards cell survival.

摘要

当NAD依赖的蛋白质脱乙酰酶Sir2过表达时，它能延长出芽酵母和线虫秀丽隐杆线虫的寿命。在秀丽隐杆线虫中，这种寿命的延长需要FOXO转录因子daf-16。最近三篇关注Sir2和FOXO哺乳动物同源物的文章强调了产生这种基因相互作用的机制。哺乳动物的SIRT1使FOXO3和/或FOXO4脱乙酰化，从而减弱FOXO诱导的细胞凋亡并增强FOXO诱导的细胞周期停滞。SIRT1可能通过将FOXO依赖的反应从细胞死亡转向细胞存活来延长寿命。