Cited by 2,081Sirtuins and Resveratrol in MedicineCancer-related Molecular PathwaysHistone Deacetylase Inhibitors Research

Negative Control of p53 by Sir2α Promotes Cell Survival under Stress

Open access
Luo, Jianyuan, Nikolaev, Anatoly Y., Imai, Shin-ichiro, Chen, Delin, Su, Fei, Shiloh, Ariel, Guarente, Leonard, Gu, Wei·2001·Cell

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 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.

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Crossref · 10.1016/s0092-8674(01)00524-4

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Authors
Luo, J., Nikolaev, A. Y., Imai, S.-I., Chen, D., Su, F., Shiloh, A., Guarente, L., & Gu, W.
Affiliations
  • Columbia University (US)
  • Massachusetts Institute of Technology (US)
Corresponding author
Gu, Wei
Venue
Cell
Publisher
Elsevier BV
Published
2001-10
Volume
107
Issue
2
Pages
137-148
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2012753961
Cited by
2,081
References
54
Citations by year
2026: 21 · 2025: 35 · 2024: 30 · 2023: 37 · 2022: 54 · 2021: 71 · 2020: 62 · 2019: 62 · 2018: 71 · 2017: 84 · 2016: 97 · 2015: 105 · 2014: 134 · 2013: 127 · 2012: 121
FWCI
39.40
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (2r01ca085533-16)
  • National Cancer Institute (R01CA85533)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
Keywords
p53, histone deacetylation, nicotinamide, p53 acetylation, apoptosis, DNA damage response, oxidative stress, stress response, cell survival, NAD+-dependent deacetylation, cancer therapy
MeSH terms
Animals, Cell Line, Cell Survival, DNA Damage, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Histone Deacetylases, Humans, NAD, Neoplasms, Niacinamide, Poly(ADP-ribose) Polymerases, Protein Binding, Blotting, Western, Transcriptional Activation, Trans-Activators, Polymerase Chain Reaction, Tumor Suppressor Protein p53, Mutagenesis, Site-Directed, Cell Death, Apoptosis, Point Mutation, Protein Structure, Tertiary, DNA, Complementary, Oxidative Stress, fas Receptor, Sirtuins, Mice, Sirtuin 1

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