The MEF2A transcription factor interactome in cardiomyocytes.

Autor: Moustafa A; Department of Biology, York University, Toronto, ON, M3J 1P3, Canada.; Muscle Health Research Centre (MHRC), York University, Toronto, ON, M3J 1P3, Canada.; Centre for Research in Biomolecular Interactions (CRBI), York University, Toronto, ON, M3J 1P3, Canada., Hashemi S; Analytical Sciences, Sanofi, Toronto, ON, M2R 3T4, Canada.; Seneca College, School of Health Sciences, King City, ON, L7B 1B3, Canada., Brar G; Department of Biology, York University, Toronto, ON, M3J 1P3, Canada.; Muscle Health Research Centre (MHRC), York University, Toronto, ON, M3J 1P3, Canada.; Centre for Research in Biomolecular Interactions (CRBI), York University, Toronto, ON, M3J 1P3, Canada., Grigull J; Department of Mathematics and Statistics, York University, Toronto, ON, M3J1P3, Canada., Ng SHS; Analytical Sciences, Sanofi, Toronto, ON, M2R 3T4, Canada.; Analytical Development, Notch Therapeutics, Toronto, ON, M5G 1M1, Canada., Williams D; Tanz Centre for Research in Neurodegenerative Diseases, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5T 0S8, Canada., Schmitt-Ulms G; Tanz Centre for Research in Neurodegenerative Diseases, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5T 0S8, Canada., McDermott JC; Department of Biology, York University, Toronto, ON, M3J 1P3, Canada. jmcderm@yorku.ca.; Muscle Health Research Centre (MHRC), York University, Toronto, ON, M3J 1P3, Canada. jmcderm@yorku.ca.; Centre for Research in Biomolecular Interactions (CRBI), York University, Toronto, ON, M3J 1P3, Canada. jmcderm@yorku.ca.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2023 Apr 05; Vol. 14 (4), pp. 240. Date of Electronic Publication: 2023 Apr 05.
DOI: 10.1038/s41419-023-05665-8
Abstrakt: Transcriptional regulators encoded by the Myocyte Enhancer Factor 2 (MEF2) gene family play a fundamental role in cardiac development, homeostasis and pathology. Previous studies indicate that MEF2A protein-protein interactions serve as a network hub in several cardiomyocyte cellular processes. Based on the idea that interactions with regulatory protein partners underly the diverse roles of MEF2A in cardiomyocyte gene expression, we undertook a systematic unbiased screen of the MEF2A protein interactome in primary cardiomyocytes using an affinity purification-based quantitative mass spectrometry approach. Bioinformatic processing of the MEF2A interactome revealed protein networks involved in the regulation of programmed cell death, inflammatory responses, actin dynamics and stress signaling in primary cardiomyocytes. Further biochemical and functional confirmation of specific protein-protein interactions documented a dynamic interaction between MEF2A and STAT3 proteins. Integration of transcriptome level data from MEF2A and STAT3-depleted cardiomyocytes reveals that the balance between MEF2A and STAT3 activity exerts a level of executive control over the inflammatory response and cardiomyocyte cell survival and experimentally ameliorates Phenylephrine induced cardiomyocyte hypertrophy. Lastly, we identified several MEF2A/STAT3 co-regulated genes, including the MMP9 gene. Herein, we document the cardiomyocyte MEF2A interactome, which furthers our understanding of protein networks involved in the hierarchical control of normal and pathophysiological cardiomyocyte gene expression in the mammalian heart.
(© 2023. The Author(s).)
Databáze: MEDLINE
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