ArticleThe Journal of physiology2013
Opposing HDAC4 nuclear fluxes due to phosphorylation by β-adrenergic activated protein kinase A or by activity or Epac activated CaMKII in skeletal muscle fibres.
Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 42 citations in OpenAlex.
- Multi-omics insight into cardiac myofibril remodeling in post-prandial Burmese pythons.Communications biology · 2026Article
- Multi-omics Insight into Cardiac Myofibril Remodeling in Post-Prandial Burmese Pythons.bioRxiv : the preprint server for biology · 2026Article
- Leucine Supplementation Counteracts the Atrophic Effects of HDAC4 in Rat Skeletal Muscle Submitted to Hindlimb Immobilization.Muscle & nerve · 2025Article
- PKA plays a conserved role in regulating gene expression and metabolic adaptation by phosphorylating Rpd3/HDAC1.Nature communications · 2025Article
- Roles of Histone Deacetylase 4 in the Inflammatory and Metabolic Processes.Diabetes & metabolism journal · 2024Review
- HDAC4 in cancer: A multitasking platform to drive not only epigenetic modifications.Frontiers in molecular biosciences · 2023Review
- Histone deacetylase 4 and 5 translocation elicited by microsecond pulsed electric field exposure is mediated by kinase activity.Frontiers in bioengineering and biotechnology · 2022Article
- CaMKII and PKA-dependent phosphorylation co-regulate nuclear localization of HDAC4 in adult cardiomyocytes.Basic research in cardiology · 2021Article
- Regulation of histone deacetylase activities and functions by phosphorylation and its physiological relevance.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- Neuronal Epac1 mediates retinal neurodegeneration in mouse models of ocular hypertension.The Journal of experimental medicine · 2020Article
- The role of histone deacetylase 4 during chondrocyte hypertrophy and endochondral bone development.Bone & joint research · 2020Review
- Functional Inhibition of Host Histone Deacetylases (HDACs) EnhancesFrontiers in immunology · 2020Article
- mAKAPβ signalosomes - A nodal regulator of gene transcription associated with pathological cardiac remodeling.Cellular signalling · 2019Review
- mTORC1 and PKB/Akt control the muscle response to denervation by regulating autophagy and HDAC4.Nature communications · 2019Article
- Coordination between Differentially Regulated Circadian Clocks Generates Rhythmic Behavior.Cold Spring Harbor perspectives in biology · 2018Review
- Bidirectional regulation of HDAC5 by mAKAPβ signalosomes in cardiac myocytes.Journal of molecular and cellular cardiology · 2018Article
- Class IIa histone deacetylases link cAMP signaling to the myelin transcriptional program of Schwann cells.The Journal of cell biology · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Novel role and regulation of HDAC4 in cocaine-related behaviors.Addiction biology · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Class IIa histone deacetylases (HDACs) move between skeletal muscle fibre cytoplasm and nuclei in response to various stimuli, suppressing activity of the exclusively nuclear transcription factor Mef2. Protein kinase A (PKA) phosphorylates class IIa HDACs in cardiac muscle, resulting in HDAC nuclear accumulation, but this has not been examined in skeletal muscle. Using HDAC4-green fluorescent protein (HDAC4-GFP) expressed in isolated skeletal muscle fibres, we now show that activation of PKA by the beta-receptor agonist isoproterenol or dibutyryl (Db) cAMP causes a steady HDAC4-GFP nuclear influx. The beta-receptor blocker propranolol or PKA inhibitor Rp-cAMPS blocks the effects of isoproterenol on the nuclear influx of HDAC4-GFP, and Rp-cAMPS blocks the effects of Db cAMP. The HDAC4-GFP construct having serines 265 and 266 replaced with alanines, HDAC4 (S265/266A)-GFP, did not respond to beta-receptor or PKA activation. Immunoprecipitation results show that HDAC4-GFP is a substrate of PKA, but HDAC4 (S265/266A)-GFP is not, implicating HDAC4 serines 265/266 as the site(s) phosphorylated by PKA. During 10 Hz trains of muscle fibre electrical stimulation, the nuclear efflux rate of HDAC4-GFP, but not of HDAC4 (S265/266)-GFP, was decreased by PKA activation, directly demonstrating antagonism between the effects of fibre stimulation and beta-adrenergic activation of PKA on HDAC4 nuclear fluxes. 8-CPT, a specific activator of Epac, caused nuclear efflux of HDAC4-GFP, opposite to the effect of PKA. Db cAMP increased both phosphorylated PKA and GTP-bound Rap1. Our results demonstrate that the PKA and CaMKII pathways play important opposing roles in skeletal muscle gene expression by oppositely affecting the subcellular localization of HDAC4.
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Registered trials
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