| First Author | Luo J | Year | 2001 |
| Journal | Cell | Volume | 107 |
| Issue | 2 | Pages | 137-48 |
| PubMed ID | 11672522 | Mgi Jnum | J:72328 |
| Mgi Id | MGI:2152474 | Doi | 10.1016/s0092-8674(01)00524-4 |
| Citation | Luo J, et al. (2001) Negative Control of p53 by Sir2alpha Promotes Cell Survival under Stress. Cell 107(2):137-48 |
| abstractText | The NAD-dependent histone deacetylation of Sir2 connects cellular metabolism with gene silencing as well as aging in yeast. Here, we show that mammalian Sir2alpha physically interacts with p53 and attenuates p53-mediated functions. Nicotinamide (Vitamin B3) inhibits an NAD-dependent p53 deacetylation induced by Sir2alpha, and also enhances the p53 acetylation levels in vivo. Furthermore, Sir2alpha represses p53-dependent apoptosis in response to DNA damage and oxidative stress, whereas expression of a Sir2alpha point mutant increases the sensitivity of cells in the stress response. Thus, our findings implicate a p53 regulatory pathway mediated by mammalian Sir2alpha. These results have significant implications regarding an important role for Sir2alpha in modulating the sensitivity of cells in p53-dependent apoptotic response and the possible effect in cancer therapy. |
