ArticleNature medicine2012
Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.
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Who cites it
122 citing papers in PubMed, 1 synthesis or guideline pooled it, 219 citations in OpenAlex.
- Histone deacetylase-mediated regulation of endolysosomal pH.The Journal of biological chemistry · 2018Pooled it
- Trichostatin A Inhibits Cytokines Released in LPS-Induced THP-1 Cells via Downregulating Deacetylated-Syntaxin 17 and Promoting Autophagosome-Lysosome Fusion.Physiological research · 2026Article
- SeSA-HCPT: A dual-targeting agent that induces DNA damage and inhibits repair for castration-resistant prostate cancer therapy.iScience · 2026Article
- HDAC4 Promotes Neuroprotection of Retinal Ganglion Cells After Optic Nerve Injury.Investigative ophthalmology & visual science · 2025Article
- Computational modeling of ATM signaling: a predictive framework for drug repurposing in ataxia-telangiectasia.NPJ systems biology and applications · 2025Article
- N-terminal oligomerization drives HDAC4 nuclear condensation and neurodevelopmental dysfunction inOpen biology · 2025Article
- ATM deficiency drives phenotypic diversity and Purkinje cell degeneration in a macaque model of ataxia-telangiectasia.Cell reports. Medicine · 2025Article
- Beyond vessels: unraveling the impact of VEGFs on neuronal functions and structure.Journal of biomedical science · 2025Review
- Upregulated astrocyte HDAC7 induces Alzheimer-like tau pathologies via deacetylating transcription factor-EB and inhibiting lysosome biogenesis.Molecular neurodegeneration · 2025Article
- Protein Phosphatase 2ACα Regulates ATR-Mediated Endogenous DNA Damage Response Against Microcephaly.Molecular neurobiology · 2025Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Axonal Regeneration after Spinal Cord Injury: Molecular Mechanisms, Regulatory Pathways, and Novel Strategies.Biology · 2024Review
- ATM Kinase Small Molecule Inhibitors Prevent Radiation-Induced Apoptosis of Mouse Neurons In Vivo.Kinases and phosphatases · 2024Article
- Roles of Histone Deacetylase 4 in the Inflammatory and Metabolic Processes.Diabetes & metabolism journal · 2024Review
- Disproportionate Expression of ATM in Cerebellar Cortex During Human Neurodevelopment.Cerebellum (London, England) · 2024Article
- ATM-deficiency-induced microglial activation promotes neurodegeneration in ataxia-telangiectasia.Cell reports · 2024Article
- Article
- BDNF and Cerebellar Ataxia.Current drug research reviews · 2024Review
- Mitochondrial stress-induced H4K12 hyperacetylation dysregulates transcription in Parkinson's disease.Frontiers in cellular neuroscience · 2024Article
- Synthesis and biological evaluation of C-4 substituted phenoxazine-bearing hydroxamic acids with potent class II histone deacetylase inhibitory activities.Journal of enzyme inhibition and medicinal chemistry · 2023Article
62 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
Abstract
Ataxia telangiectasia is a neurodegenerative disease caused by mutation of the Atm gene. Here we report that ataxia telangiectasia mutated (ATM) deficiency causes nuclear accumulation of histone deacetylase 4 (HDAC4) in neurons and promotes neurodegeneration. Nuclear HDAC4 binds to chromatin, as well as to myocyte enhancer factor 2A (MEF2A) and cAMP-responsive element binding protein (CREB), leading to histone deacetylation and altered neuronal gene expression. Blocking either HDAC4 activity or its nuclear accumulation blunts these neurodegenerative changes and rescues several behavioral abnormalities of ATM-deficient mice. Full rescue of the neurodegeneration, however, also requires the presence of HDAC4 in the cytoplasm, suggesting that the ataxia telangiectasia phenotype results both from a loss of cytoplasmic HDAC4 as well as its nuclear accumulation. To remain cytoplasmic, HDAC4 must be phosphorylated. The activity of the HDAC4 phosphatase, protein phosphatase 2A (PP2A), is downregulated by ATM-mediated phosphorylation. In ATM deficiency, enhanced PP2A activity leads to HDAC4 dephosphorylation and the nuclear accumulation of HDAC4. Our results define a crucial role of the cellular localization of HDAC4 in the events leading to ataxia telangiectasia neurodegeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.