| First Author | Wang C | Year | 2006 |
| Journal | Nat Cell Biol | Volume | 8 |
| Issue | 9 | Pages | 1025-31 |
| PubMed ID | 16892051 | Mgi Jnum | J:178276 |
| Mgi Id | MGI:5297785 | Doi | 10.1038/ncb1468 |
| Citation | Wang C, et al. (2006) Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol 8(9):1025-31 |
| abstractText | 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. |
