The Interaction Between FOXO and SIRT1: Tipping the Balance Towards Survival

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Survival / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Sirtuin 1
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Drosophila Proteins
  • FOXO protein, Drosophila
  • FOXO4 protein, human
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • FoxO3 protein, mouse
  • Transcription Factors
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins
  • Histone Deacetylases