Journal article
14-3-3 epsilon Plays a Role in Cardiac Ventricular Compaction by Regulating the Cardiomyocyte Cell Cycle
Molecular and cellular biology, v 32(24), pp 5089-5102
01 Dec 2012
PMID: 23071090
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Trabecular myocardium accounts for the majority of the ventricles during early cardiogenesis, but compact myocardium is the primary component at later developmental stages. Elucidation of the genes regulating compact myocardium development is essential to increase our understanding of left ventricular noncompaction (LVNC), a cardiomyopathy characterized by increased ratios of trabecular to compact myocardium. 14-3-3 epsilon is an adapter protein expressed in the lateral plate mesoderm, but its in vivo cardiac functions remain to be defined. Here we show that 14-3-3 epsilon is expressed in the developing mouse heart as well as in cardiomyocytes. 14-3-3 epsilon deletion did not appear to induce compensation by other 14-3-3 isoforms but led to ventricular noncompaction, with features similar to LVNC, resulting from a selective reduction in compact myocardium thickness. Abnormal compaction derived from a 50% decrease in cardiac proliferation as a result of a reduced number of cardiomyocytes in G(2)/M and the accumulation of cardiomyocytes in the G(0)/G(1) phase of the cell cycle. These defects originated from downregulation of cyclin E1 and upregulation of p27(Kip1), possibly through both transcriptional and posttranslational mechanisms. Our work shows that 14-3-3 epsilon regulates cardiogenesis and growth of the compact ventricular myocardium by modulating the cardiomyocyte cell cycle via both cyclin E1 and p27(Kip1). These data are consistent with the long-held view that human LVNC may result from compaction arrest, and they implicate 14-3-3 epsilon as a new candidate gene in congenital human cardiomyopathies.
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Details
- Title
- 14-3-3 epsilon Plays a Role in Cardiac Ventricular Compaction by Regulating the Cardiomyocyte Cell Cycle
- Creators
- Yasuhiro Kosaka - University of UtahKatarzyna A. Cieslik - Baylor College of MedicineLing Li - University of UtahGeorge Lezin - University of UtahColin T. Maguire - University of UtahYukio Saijoh - University of UtahKazuhito Toyo-oka - University of California, San FranciscoMichael J. Gambello - Emory UniversityMatteo Vatta - Baylor College of MedicineAnthony Wynshaw-Boris - University of California, San FranciscoAntonio Baldini - National Research CouncilH. Joseph Yost - University of UtahLuca Brunelli - University of Utah
- Publication Details
- Molecular and cellular biology, v 32(24), pp 5089-5102
- Publisher
- Amer Soc Microbiology
- Number of pages
- 14
- Grant note
- Division of Neonatology (Pediatrics), University of Utah School of Medicine Children's Health Research Center, University of Utah School of Medicine R01HD066121 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Primary Children's Medical Center Foundation Innovative Grant at the University of Utah School of Medicine American Heart Association 8UL1TR000105 / National Center for Research Resources, National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) 8UL1TR000105 / National Center for Advancing Translational Sciences, National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) UL1RR025764 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) National Institute of Child Health and Human Development; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Department of Pediatrics (Neonatology), The University of Texas Medical School at Houston
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000311492200018
- Scopus ID
- 2-s2.0-84871908867
- Other Identifier
- 991020100083804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology