期刊
CELLULAR SIGNALLING
卷 63, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2019.109357
关键词
Kinase; AKAP; Gene transcription; Cardiac hypertrophy; cAMP
类别
资金
- National Institutes of Health [HL126825, HL146111, HL126950, EY026766]
- California Tobacco-Related Disease Research Grants Program Office of the University of California [27IR-0045]
- American Heart Association [18PRE34030209]
Striated myocytes compose about half of the cells of the heart, while contributing the majority of the heart's mass and volume. In response to increased demands for pumping power, including in diseases of pressure and volume overload, the contractile myocytes undergo non-mitotic growth, resulting in increased heart mass, i.e. cardiac hypertrophy. Myocyte hypertrophy is induced by a change in the gene expression program driven by the altered activity of transcription factors and co-repressor and co-activator chromatin-associated proteins. These gene regulatory proteins are subject to diverse post-translational modifications and serve as nuclear effectors for intracellular signal transduction pathways, including those controlled by cyclic nucleotides and calcium ion. Scaffold proteins contribute to the underlying architecture of intracellular signaling networks by targeting signaling enzymes to discrete intracellular compartments, providing specificity to the regulation of downstream effectors, including those regulating gene expression. Muscle A-kinase anchoring protein beta (mAKAP beta) is a well characterized scaffold protein that contributes to the regulation of pathological cardiac hypertrophy. In this review, we discuss the mechanisms how this prototypical scaffold protein organizes signalosomes responsible for the regulation of class Ha histone deacetylases and cardiac transcription factors such as NFAT, MEF2, and HIF-1 alpha, as well as how this signalosome represents a novel therapeutic target for the prevention or treatment of heart failure.
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