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PubMed · 16892051

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
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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-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.

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ApoptosisCell LineCell Line, TumorDNA DamageE2F1 Transcription FactorEtoposideFeedback, PhysiologicalHumansMutationProtein BindingRNA, Small InterferingSirtuin 1SirtuinsJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't

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Chuangui Wang, Lihong Chen, Xinghua Hou, Zhenyu Li, Neha Kabra, Yihong Ma, Shino Nemoto, Toren Finkel, Wei Gu, W Douglas Cress, Jiandong Chen. 2006-08-06. Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage.. https://doi.org/10.1038/ncb1468

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