ArticleGenes & development2005
Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4.
Article in Genes & development, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 2 of them syntheses that pooled it.
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Who cites it
124 citing papers in PubMed, 2 syntheses or guidelines pooled it, 227 citations in OpenAlex.
- Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.PLoS genetics · 2019Pooled it
- Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region.Annals of the rheumatic diseases · 2013Pooled it
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- Adenylosuccinate Synthase 1 Deficiency Improves Energy Metabolism by Promoting Adipose Tissue Re-esterification via Glycerol Kinase Upregulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Butyrate-producing commensal bacteria confers colon immune defense function via enhancing H4K31 Crotonylation of macrophages.Microbiome · 2025Article
- Epigenetic dysregulation of energy homeostasis drives aortic valve stenosis that is treatable with metformin.JCI insight · 2025Article
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- Transcriptional Repression of CCL2 by KInternational journal of molecular sciences · 2025Article
- HDAC3 Serine 424 Phospho-mimic and Phospho-null Mutants Bidirectionally Modulate Long-Term Memory Formation and Synaptic Plasticity in the Adult and Aging Mouse Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- CK2B Induces CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Role of HDAC3 in Pulmonary Diseases.Lung · 2025Review
- PRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cells.Journal of translational medicine · 2025Article
- Comparative Proteomic Identification of Ram Sperm before and after In Vitro Capacitation.Animals : an open access journal from MDPI · 2024Article
- Protein phosphatase 4 dephosphorylates phosphofructokinase-1 to regulate its enzymatic activity.BMB reports · 2023Article
- Separation of transcriptional repressor and activator functions in Drosophila HDAC3.Development (Cambridge, England) · 2023Article
- Confined migration induces heterochromatin formation and alters chromatin accessibility.iScience · 2022Article
- UL34 Deletion Restricts Human Cytomegalovirus Capsid Formation and Maturation.International journal of molecular sciences · 2022Article
- The druggable schizophrenia genome: from repurposing opportunities to unexplored drug targets.NPJ genomic medicine · 2022Review
- Bisphenol A replacement chemicals, BPF and BPS, induce protumorigenic changes in human mammary gland organoid morphology and proteome.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- High expression of CCDC6 in relation to unfavorable outcome and immune cells infiltration in hepatobiliary carcinoma.Journal of Cancer · 2022Article
64 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 3 (HDAC3) is one of four members of the human class I HDACs that regulates gene expression by deacetylation of histones and nonhistone proteins. Early studies have suggested that HDAC3 activity is regulated by association with the corepressors N-CoR and SMRT. Here we demonstrate that, in addition to protein-protein interactions with NCoR/SMRT, the activity of HDAC3 is regulated by both phosphorylation and dephosphorylation. A protein kinase CK2 phosphoacceptor site in the HDAC3 protein was identified at position Ser424, which is a nonconserved residue among the class I HDACs. Mutation of this residue was found to reduce deacetylase activity. Interestingly, unlike other class I HDACs, HDAC3 uniquely copurifies with the catalytic and regulatory subunits of the protein serine/threonine phosphatase 4 complex (PP4c/PP4R1). Furthermore, HDAC3 complexes displayed protein phosphatase activity and a series of subsequent mutational analyses revealed that the N terminus of HDAC3 (residues 1-122) was both necessary and sufficient for HDAC3-PP4c interactions. Significantly, both overexpression and siRNA knock-down approaches, and analysis of cells devoid of PP4c, unequivocally show that HDAC3 activity is inversely proportional to the cellular abundance of PP4(c). These findings therefore further highlight the importance of protein-protein interactions and extend the significance of dephosphorylation in the regulation of HDAC activity, as well as present a novel alternative pathway by which HDAC3 activity is regulated.
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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.