Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage

• Autores: Chuangui Wang, Neha Kabra, Toren Finkel, Wei Gu, W. Douglas Cress
• Localización: Nature: Cell biology, ISSN 1465-7392, Nº. 9, 2006, págs. 1025-1031
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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.