Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage

Chuangui Wang, Lihong Chen, Xinghua Hou, Zhenyu Li, Neha Kabra, Yihong Ma, Shino Nemoto, Toren Finkel, Wei Gu, W. Douglas Cress, Jiandong Chen

Research output: Contribution to journalArticlepeer-review

Abstract

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-κB 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.

Original languageEnglish (US)
Pages (from-to)1025-1031
Number of pages7
JournalNature Cell Biology
Volume8
Issue number9
DOIs
StatePublished - Sep 2006
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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