Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage

Nat Cell Biol. 2006 Sep;8(9):1025-31. doi: 10.1038/ncb1468. Epub 2006 Aug 6.


The nicotinamide adenine dinucleotide (NAD)-dependent deacetylase Sir2 (silent information regulator 2) regulates gene silencing in yeast and promotes lifespan extension during caloric restriction. The mammalian homologue of Sir2 (SirT1) regulates p53, NF-kappaB and Forkhead transcription factors, and is implicated in stress response. This report shows that the cell-cycle and apoptosis regulator E2F1 induces SirT1 expression at the transcriptional level. Furthermore, SirT1 binds to E2F1 and inhibits E2F1 activities, forming a negative feedback loop. Knockdown of SirT1 by small interference RNA (siRNA) increases E2F1 transcriptional and apoptotic functions. DNA damage by etoposide causes E2F1-dependent induction of SirT1 expression and knockdown of SirT1 increases sensitivity to etoposide. These results reveal a mutual regulation between E2F1 and SirT1 that affects cellular sensitivity to DNA damage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Line
  • Cell Line, Tumor
  • DNA Damage*
  • E2F1 Transcription Factor / metabolism*
  • Etoposide / toxicity
  • Feedback, Physiological
  • Humans
  • Mutation
  • Protein Binding
  • RNA, Small Interfering / genetics
  • Sirtuin 1
  • Sirtuins / genetics
  • Sirtuins / metabolism*


  • E2F1 Transcription Factor
  • E2F1 protein, human
  • RNA, Small Interfering
  • Etoposide
  • SIRT1 protein, human
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Sirtuins