ArticleMolecular and cellular biology2004
Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 288 papers.
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Who cites it
288 citing papers in PubMed, 515 citations in OpenAlex.
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- The multifactorial role of HDAC9 at the maternal-fetal interface in the pathogenesis of preeclampsia.Clinical science (London, England : 1979) · 2025Review
- Deciphering the Role of Different Ceramide Synthases in the Human Cardiomyocyte Hypertrophic Response.Metabolites · 2025Article
- HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.Cells · 2025Review
- Acetylation in Cardiac Aging: Molecular Mechanism and Therapeutic Approaches.Results and problems in cell differentiation · 2025Review
- Sex-specific regulation of the cardiac transcriptome by the protein phosphatase 2A regulatory subunit B55α.npj metabolic health and disease · 2024Article
- Effect of deletion of the protein kinase PRKD1 on development of the mouse embryonic heart.Journal of anatomy · 2024Article
- HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction.Orphanet journal of rare diseases · 2023Article
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- Structural insights into regulation of the PEAK3 pseudokinase scaffold by 14-3-3.Nature communications · 2023Article
- HDAC8 regulates protein kinase D phosphorylation in skeletal myoblasts in response to stress signaling.Biochemical and biophysical research communications · 2023Article
- Statins inhibit protein kinase D (PKD) activation in intestinal cells and prevent PKD1-induced growth of murine enteroids.American journal of physiology. Cell physiology · 2023Article
- Small Molecule Inhibitors of Protein Kinase D: Early Development, Current Approaches, and Future Directions.Journal of medicinal chemistry · 2023Review
- Metabolic remodeling in cardiac hypertrophy and heart failure with reduced ejection fraction occurs independent of transcription factor EB in mice.Frontiers in cardiovascular medicine · 2023Article
- Protein phosphatase 1 regulates reactive oxygen species-dependent degradation of histone deacetylase 5 by intermittent hypoxia.American journal of physiology. Cell physiology · 2022Article
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- Sex Differences in Psychostimulant Abuse: Implications for Estrogen Receptors and Histone Deacetylases.Genes · 2022Review
- Spatial and temporal dynamics of HDACs class IIa following mild traumatic brain injury in adult rats.Molecular psychiatry · 2022Article
- EGCG prevents pressure overload‑induced myocardial remodeling by downregulating overexpression of HDAC5 in mice.International journal of molecular medicine · 2022Article
228 more citing papers are in PubMed but not listed here.
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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
A variety of stress signals stimulate cardiac myocytes to undergo hypertrophy. Persistent cardiac hypertrophy is associated with elevated risk for the development of heart failure. Recently, we showed that class II histone deacetylases (HDACs) suppress cardiac hypertrophy and that stress signals neutralize this repressive function by triggering phosphorylation- and CRM1-dependent nuclear export of these chromatin-modifying enzymes. However, the identities of cardiac HDAC kinases have remained unclear. Here, we demonstrate that signaling by protein kinase C (PKC) is sufficient and, in some cases, necessary to drive nuclear export of class II HDAC5 in cardiomyocytes. Inhibition of PKC prevents nucleocytoplasmic shuttling of HDAC5 in response to a subset of hypertrophic agonists. Moreover, a nonphosphorylatable HDAC5 mutant is refractory to PKC signaling and blocks cardiomyocyte hypertrophy mediated by pharmacological activators of PKC. We also demonstrate that protein kinase D (PKD), a downstream effector of PKC, directly phosphorylates HDAC5 and stimulates its nuclear export. These findings reveal a novel function for the PKC/PKD axis in coupling extracellular cues to chromatin modifications that control cellular growth, and they suggest potential utility for small-molecule inhibitors of this pathway in the treatment of pathological cardiac gene expression.
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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 Socratic graph.