|
Título:
|
Translation of Myocyte Enhancer Factor-2 is induced by hypertrophic stimuli in cardiomyocytes through a Calcineurin-dependent pathway
|
|
Autor/a:
|
Ye, Junmei; Cardona, Maria; Llovera i Tomàs, Marta; Comella i Carnicé, Joan Xavier; Sanchis, Daniel
|
|
Notas:
|
The 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.
This 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. |
|
Materia(s):
|
-Cardiomyocyte
-Hypertrophy
-Myocyte Enhancer Factor-2 |
|
Derechos:
|
(c) Elsevier, 2012
info:eu-repo/semantics/restrictedAccess |
|
Tipo de documento:
|
article
publishedVersion |
|
Editor:
|
Elsevier
|
|
Compartir:
|
|
