Regulation of c-jun mRNA expression in adult cardiocytes by MAP kinase interacting kinase-1 (MNK1).

Hypertrophic growth of adult myocardium is associated with increased expression of the early response gene c-jun. The purpose of this study was to determine whether eukaryotic initiation factor (elF) 4E (eIF4E) regulates translational efficiency of c-jun mRNA as measured by flux into polysomes. Adult feline cardiomyocytes in primary culture were treated with 0.2 microM 12-O-tetradecanoylphorbol 13-acetate (TPA), and c-jun mRNA was quantified in total, monosome, and polysome fractions by real-time polymerase chain reaction. After 1 h, TPA increased total c-jun mRNA by 10.5-fold. The corresponding flux into polysomes was significantly lower (5-fold). Adenoviral-mediated overexpression of either eIF4E or a nonphosphorylatable mutant (S209/A) did not affect total c-jun mRNA or its flux between monosomes and polysomes. Similar results were obtained following overexpression of the eIF4E kinase Mnk1. Thus, translational efficiency of c-jun mRNA was not affected by changes in activity or amount of eIF4E. In contrast, a kinase-deficient Mnk1 mutant significantly reduced total c-jun mRNA from 9.8-fold to 6.0-fold while flux between monosomes and polysomes remained constant. The decrease in total c-jun mRNA resulted from increased decay of c-jun mRNA incorporated into the polysomes. We conclude that Mnk1 activity stabilizes c-jun mRNA in polysomes independent of eIF4E phosphorylation.