Dataset Information

Bidirectional regulation of HDAC5 by mAKAP? signalosomes in cardiac myocytes.

ABSTRACT: Class IIa histone deacetylases (HDACs) are transcriptional repressors whose nuclear export in the cardiac myocyte is associated with the induction of pathological gene expression and cardiac remodeling. Class IIa HDACs are regulated by multiple, functionally opposing post-translational modifications, including phosphorylation by protein kinase D (PKD) that promotes nuclear export and phosphorylation by protein kinase A (PKA) that promotes nuclear import. We have previously shown that the scaffold protein muscle A-kinase anchoring protein ? (mAKAP?) orchestrates signaling in the cardiac myocyte required for pathological cardiac remodeling, including serving as a scaffold for both PKD and PKA. We now show that mAKAP? is a scaffold for HDAC5 in cardiac myocytes, forming signalosomes containing HDAC5, PKD, and PKA. Inhibition of mAKAP? expression attenuated the phosphorylation of HDAC5 by PKD and PKA in response to ?- and ?-adrenergic receptor stimulation, respectively. Importantly, disruption of mAKAP?-HDAC5 anchoring prevented the induction of HDAC5 nuclear export by ?-adrenergic receptor signaling and PKD phosphorylation. In addition, disruption of mAKAP?-PKA anchoring prevented the inhibition by ?-adrenergic receptor stimulation of ?-adrenergic-induced HDAC5 nuclear export. Together, these data establish that mAKAP? signalosomes serve to bidirectionally regulate the nuclear-cytoplasmic localization of class IIa HDACs. Thus, the mAKAP? scaffold serves as a node in the myocyte regulatory network controlling both the repression and activation of pathological gene expression in health and disease, respectively.

SUBMITTER: Dodge-Kafka KL

PROVIDER: S-EPMC5940533 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Bidirectional regulation of HDAC5 by mAKAPβ signalosomes in cardiac myocytes.

Dodge-Kafka Kimberly L KL Gildart Moriah M Li Jinliang J Thakur Hrishikesh H Kapiloff Michael S MS

Journal of molecular and cellular cardiology 20180306

Class IIa histone deacetylases (HDACs) are transcriptional repressors whose nuclear export in the cardiac myocyte is associated with the induction of pathological gene expression and cardiac remodeling. Class IIa HDACs are regulated by multiple, functionally opposing post-translational modifications, including phosphorylation by protein kinase D (PKD) that promotes nuclear export and phosphorylation by protein kinase A (PKA) that promotes nuclear import. We have previously shown that the scaffol ...[more]

PMID: 29522762

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Dataset Information

Bidirectional regulation of HDAC5 by mAKAP? signalosomes in cardiac myocytes.

Publications

Bidirectional regulation of HDAC5 by mAKAPβ signalosomes in cardiac myocytes.

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