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.
Spruill
Laura S
LS
Department of Medicine, The Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston, South Carolina 29403, USA.
McDermott
Paul J
PJ
D000818:Animals; D002415:Cats; D002478:Cells, Cultured; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011132:Polyribosomes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics*
D039561:Eukaryotic Initiation Factor-4E; D047908:Intracellular Signaling Peptides and Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases