The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Protein Kinases C and D Mediate Agonist-Dependent Cardiac Hypertrophy through Nuclear Export of Histone Deacetylase 5
Open accessAbstract
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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Self-citationCardiac Hypertrophy: The Good, the Bad, and the Ugly
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Self-citationSignal-dependent nuclear export of a histone deacetylase regulates muscle differentiation
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Self-citationClass II Histone Deacetylases Act as Signal-Responsive Repressors of Cardiac Hypertrophy
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Self-citationThree proteins define a class of human histone deacetylases related to yeast Hda1p
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Self-citationInhibition of protein kinase C μ by various inhibitors. Inhibition from protein kinase c isoenzymes
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PKC-α regulates cardiac contractility and propensity toward heart failure
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Cited by
Regulation of cardiac hypertrophy by intracellular signalling pathways
Heineke, J., & Molkentin, J. D. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1983 · Cited by 1,866
Calcium Cycling and Signaling in Cardiac Myocytes
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The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men
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HDAC family: What are the cancer relevant targets?
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Signaling Pathways in Skeletal Muscle Remodeling
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Metadata
- Authors
- Vega, R. B., Harrison, B. C., Meadows, E., Roberts, C. R., Papst, P. J., Olson, E. N., & McKinsey, T. A.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-10-01
- Volume
- 24
- Issue
- 19
- Pages
- 8374-8385
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2099959808
- Cited by
- 511
- References
- 47
- FWCI
- 9.51
- Type
- journal article
- Language
- en
- Open access
- green
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- Vega, R. B., Harrison, B. C., Meadows, E., Roberts, C. R., Papst, P. J., Olson, E. N., & McKinsey, T. A. (2004). Protein Kinases C and D Mediate Agonist-Dependent Cardiac Hypertrophy through Nuclear Export of Histone Deacetylase 5. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.24.19.8374-8385.2004
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