Negative control of p53 by Sir2α promotes cell survival under stress

Jianyuan Luo, Anatoly Y. Nikolaev, Shin ichiro Imai, Delin Chen, Fei Su, Ariel Shiloh, Leonard Guarente, Wei Gu

Research output: Contribution to journalArticlepeer-review

1742 Scopus citations

Abstract

The NAD-dependent histone deacetylation of Sir2 connects cellular metabolism with gene silencing as well as aging in yeast. Here, we show that mammalian Sir2α physically interacts with p53 and attenuates p53-mediated functions. Nicotinamide (Vitamin B3) inhibits an NAD-dependent p53 deacetylation induced by Sir2α, and also enhances the p53 acetylation levels in vivo. Furthermore, Sir2α represses p53-dependent apoptosis in response to DNA damage and oxidative stress, whereas expression of a Sir2α point mutant increases the sensitivity of cells in the stress response. Thus, our findings implicate a p53 regulatory pathway mediated by mammalian Sir2α. These results have significant implications regarding an important role for Sir2α in modulating the sensitivity of cells in p53-dependent apoptotic response and the possible effect in cancer therapy.

Original languageEnglish (US)
Pages (from-to)137-148
Number of pages12
JournalCell
Volume107
Issue number2
DOIs
StatePublished - Oct 19 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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