ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Specific acetylation of p53 by HDAC inhibition prevents DNA damage-induced apoptosis in neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 95 citations in OpenAlex.
- Targeting mutant p53 in cancer: from mechanistic insights to therapeutic strategies.Cellular & molecular biology letters · 2026Review
- Epigenetic Regulation in Ischemic Neuroprotection: The Dual Role of HDACs and HATs in Neuroinflammation and Recovery.Antioxidants (Basel, Switzerland) · 2025Review
- Purple Corn Extract Prevents Doxo-Induced Cardiotoxicity by Counteracting AMPK Activation and p53 Acetylation in HL-1 and Primary Cardiomyocytes.Oxidative medicine and cellular longevity · 2025Article
- From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.Biomarker research · 2024Review
- Preservation of Murine Whole Eyes With Supplemented UW Cold Storage Solution: Anatomical Considerations.Translational vision science & technology · 2024Article
- Article
- Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- Rbbp4 loss disrupts neural progenitor cell cycle regulation independent of Rb and leads to Tp53 acetylation and apoptosis.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Fasting induces a highly resilient deep quiescent state in muscle stem cells via ketone body signaling.Cell metabolism · 2022Article
- SIRT1: Genetic Variants and Serum Levels in Age-Related Macular Degeneration.Life (Basel, Switzerland) · 2022Article
- Sirt1 overexpression attenuates Western-style diet-induced aortic stiffening in mice.Physiological reports · 2022Article
- Activation of SIRT-1 Signalling in the Prevention of Bipolar Disorder and Related Neurocomplications: Target Activators and Influences on Neurological Dysfunctions.Neurotoxicity research · 2022Review
- Association of SIRT1 single gene nucleotide polymorphisms and serum SIRT1 levels with laryngeal squamous cell carcinoma patient survival rate.Cancer biomarkers : section A of Disease markers · 2022Article
- Histone acetylation modifications: A potential targets for the diagnosis and treatment of papillary thyroid cancer.Frontiers in oncology · 2022Review
- Upregulation of ERK-EGR1-heparanase axis by HDAC inhibitors provides targets for rational therapeutic intervention in synovial sarcoma.Journal of experimental & clinical cancer research : CR · 2021Article
- Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration.Antioxidants (Basel, Switzerland) · 2021Review
- Dexmedetomidine Ameliorates Postoperative Cognitive Dysfunction via the MicroRNA-381-Mediated EGR1/p53 Axis.Molecular neurobiology · 2021Article
- Increased Susceptibility and Intrinsic Apoptotic Signaling in Neurons by Induced HDAC3 Expression.Investigative ophthalmology & visual science · 2021Article
- Novel perspectives for neurodegeneration prevention: effects of bioactive polyphenols.Neural regeneration research · 2021Article
- Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells.Archives of toxicology · 2021Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Histone deacetylase (HDAC) inhibitors have been used to promote neuronal survival and ameliorate neurological dysfunction in a host of neurodegenerative disease models. The precise molecular mechanisms whereby HDAC inhibitors prevent neuronal death are currently the focus of intensive research. Here we demonstrate that HDAC inhibition prevents DNA damage-induced neurodegeneration by modifying the acetylation pattern of the tumor suppressor p53, which decreases its DNA-binding and transcriptional activation of target genes. Specifically, we identify that acetylation at K382 and K381 prevents p53 from associating with the pro-apoptotic PUMA gene promoter, activating transcription, and inducing apoptosis in mouse primary cortical neurons. Paradoxically, acetylation of p53 at the same lysines in various cancer cell lines leads to the induction of PUMA expression and death. Together, our data provide a molecular understanding of the specific outcomes of HDAC inhibition and suggest that strategies aimed at enhancing p53 acetylation at K381 and K382 might be therapeutically viable for capturing the beneficial effects in the CNS, without compromising tumor suppression.
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