Translation of Myocyte Enhancer Factor-2 is induced by hypertrophic stimuli in cardiomyocytes through a Calcineurin-dependent pathway

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dc.contributor.authorYe, Junmei
dc.contributor.authorCardona, Maria
dc.contributor.authorLlovera i Tomàs, Marta
dc.contributor.authorComella i Carnicé, Joan Xavier
dc.contributor.authorSanchis, Daniel
dc.date.accessioned2016-05-23T09:52:39Z
dc.date.embargoEndDate2025-01-01
dc.date.issued2012
dc.description.abstractThe Myocyte Enhancer Factor-2 (MEF2) family of transcription factors regulates gene expression during cardiomyocyte differentiation and adaptation of the myocardium to stress. MEF2 activity is enhanced by increasing its transcription and by MAPK-dependent phosphorylation, and is reduced by binding to class-II Histone Deacetylases and by miR-1-mediated degradation of its transcript. Here we show that MEF2 protein abundance is regulated at the translational level, determining myocyte size, during hypertrophy. In order to reduce MEF2 protein expression, its silencing through RNA interference required serum deprivation and, even in this condition, MEF2 protein abundance recovered to basal levels in presence of phenylephrine. Hypertrophic agonist stimulation of neonatal ventricular cardiomyocytes increased Mef2 expression by enhancing its translation, without changing its transcription or blocking degradation of the protein. MEF2 abundance was increased by Calcineurin overexpression in vivo and was reduced by Calcineurin inhibition in vitro, without affecting Mef2 mRNA levels. Calcineurin activity influenced expression of Polypyrimidine Tract Protein (PTB), contributing to MEF2 translation. Thus, our results show a previously unrecognized but relevant level of MEF2 activity regulation through the control of its translation that involves Calcineurin and PTB.ca_ES
dc.description.sponsorshipThis work was supported by grant SAF2010_19125 from the Ministerio de Innovación y Ciencia of Spain (MICINN, now Ministerio de Economía y Competitividad) to DS and by the Agencia de Gestió d'Ajuts a Grups de Recerca (AGAUR) from the Generalitat de Catalunya 2009SGR-346 to DS and JXC. JY is a recipient of a fellowship from the Universitat de Lleida (Spain) and MC has a FPU (Formación de profesorado universitario) fellowship from MICINN.ca_ES
dc.identifier.doihttps://doi.org/10.1016/j.yjmcc.2012.07.013
dc.identifier.idgrec018064
dc.identifier.issn0022-2828
dc.identifier.urihttp://hdl.handle.net/10459.1/57084
dc.language.isoengca_ES
dc.publisherElsevierca_ES
dc.relationMICINN/PN2008-2011/SAF2010-19125
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1016/j.yjmcc.2012.07.013ca_ES
dc.relation.ispartofJournal of Molecular and Cellular Cardiology, 2012, vol. 53, núm. 4, p. 578-587ca_ES
dc.rights(c) Elsevier, 2012ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.subjectCardiomyocyteca_ES
dc.subjectHypertrophyca_ES
dc.subjectMyocyte Enhancer Factor-2ca_ES
dc.titleTranslation of Myocyte Enhancer Factor-2 is induced by hypertrophic stimuli in cardiomyocytes through a Calcineurin-dependent pathwayca_ES
dc.typearticleca_ES
dc.type.versionpublishedVersionca_ES
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