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.