Differential Activation of P-TEFb Complexes in the Development of Cardiomyocyte Hypertrophy following Activation of Distinct G Protein-Coupled Receptors.

ABSTRACT: Pathological cardiac hypertrophy is driven by neurohormonal activation of specific G protein-coupled receptors (GPCRs) in cardiomyocytes and is accompanied by large-scale changes in cardiomyocyte gene expression. These transcriptional changes require activity of positive transcription elongation factor b (P-TEFb), which is recruited to target genes by the bromodomain protein Brd4 or the super elongation complex (SEC). Here, we describe GPCR-specific regulation of these P-TEFb complexes and a novel mechanism for activating Brd4 in primary neonatal rat cardiomyocytes. The SEC was required for the hypertrophic response downstream of either the α₁-adrenergic receptor (α₁-AR) or the endothelin receptor (ETR). In contrast, Brd4 inhibition selectively impaired the α₁

SUBMITTER: Martin RD 

PROVIDER: S-EPMC7324848 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature