ArticleMolecular and cellular biology2006
Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 262 papers.
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Who cites it
262 citing papers in PubMed, 486 citations in OpenAlex.
- Roles of Sirtuin-1 in the Prevention of Intracranial Aneurysm Rupture in Mice.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Differential Modulation of Extracellular Matrix- and Longevity-Related Gene Expression by Calcium Hydroxylapatite Formulations.Life (Basel, Switzerland) · 2026Article
- VEGF inhibitor-induced vascular dysfunction involves redox-sensitive PARP activation and SIRT1 disruption.Experimental physiology · 2026Article
- Cellular Senescence Triggered by Food and Environmental Genotoxins.International journal of molecular sciences · 2026Review
- Propofol and Salvianolic Acid a Synergistically Attenuate LPS-Induced Myocardial Pyroptosis in Diabetic Mice via the SIRT1/HMGB1 Pathway.Mediators of inflammation · 2026Article
- Trichosanthes kirilowii Maximowicz attenuates dexamethasone induced atrophy in C2C12 myotubes through a Sirtuin 1 associated mechanism.Scientific reports · 2025Article
- Integrated Multiomics Analysis and Mendelian Randomization Identify SIRT1 as a Pivotal Aging-Associated Gene in Meningioma.IUBMB life · 2025Article
- Dimeric guaianolide sesquiterpenoids from the flowers of Chrysanthemum indicum ameliorate hepatic steatosis through mitigating SIRT1-mediated lipid accumulation and ferroptosis.Journal of advanced research · 2025Article
- Can Sirtuin 1 Serve as a Therapeutic Target in Pulmonary Arterial Hypertension? A Comprehensive Review.Molecules (Basel, Switzerland) · 2025Review
- Effect of Estrogen on Sirt1 Signaling in Human Macrophages.International journal of molecular sciences · 2025Article
- Sirtuin 1 Activation Mitigates Murine Vasculitis Severity by Promoting Autophagy and Mitophagy.bioRxiv : the preprint server for biology · 2025Article
- SIRT1-Mediated Redox and Senescence Regulation in Cancer: Mechanisms and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2025Review
- Reactive oxygen species regulate adipose-osteogenic lineage commitment of human mesenchymal stem cells by modulating gene expression of C/EBP homology protein and aldo-keto reductase family 1 member A1.Cell & bioscience · 2025Article
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- Regulation of HDAC6 Catalytic Activity in Cancer: The Role of Post-Translational Modifications and Protein-Protein Interactions.International journal of molecular sciences · 2025Review
- Sirtuin-1 Regulates Mitochondrial Calcium Uptake Through Mitochondrial Calcium Uptake 1 (MICU1).Life (Basel, Switzerland) · 2025Article
- Epigenetic regulation of histone 3 acetylation and p53 by SIRT1 overexpression in an experimental model of alveolar epithelium damage.Journal of biosciences · 2025Article
- Acetylresveratrol (AC-Res): An Evolving Frontier in Modulating Gene Expression.Current gene therapy · 2025Review
- NMN reverses D-galactose-induced neurodegeneration and enhances the intestinal barrier of mice by activating the Sirt1 pathway.Frontiers in pharmacology · 2025Article
- EX527, a sirtuins 1 inhibitor, sensitizes T-cell leukemia to death receptor-mediated apoptosis by downregulating cellular FLICE inhibitory protein.Cancer biology & therapy · 2024Article
202 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human SIRT1 is an enzyme that deacetylates the p53 tumor suppressor protein and has been suggested to modulate p53-dependent functions including DNA damage-induced cell death. In this report, we used EX-527, a novel, potent, and specific small-molecule inhibitor of SIRT1 catalytic activity to examine the role of SIRT1 in p53 acetylation and cell survival after DNA damage. Treatment with EX-527 dramatically increased acetylation at lysine 382 of p53 after different types of DNA damage in primary human mammary epithelial cells and several cell lines. Significantly, inhibition of SIRT1 catalytic activity by EX-527 had no effect on cell growth, viability, or p53-controlled gene expression in cells treated with etoposide. Acetyl-p53 was also increased by the histone deacetylase (HDAC) class I/II inhibitor trichostatin A (TSA). EX-527 and TSA acted synergistically to increase acetyl-p53 levels, confirming that p53 acetylation is regulated by both SIRT1 and HDACs. While TSA alone reduced cell survival after DNA damage, the combination of EX-527 and TSA had no further effect on cell viability and growth. These results show that, although SIRT1 deacetylates p53, this does not play a role in cell survival following DNA damage in certain cell lines and primary human mammary epithelial cells.
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