Current accepted models suggest that hypophosphorylated 4E-binding protein (4E-BP1) binds to initiation<br/>factor 4E (eIF4E) to inhibit cap-dependent translation, a process readily reversed by its phosphorylation<br/>following activation of mammalian target of rapamycin (mTORC1) signalling. Myogenic differentiation in the<br/>C2C12 myoblast model system reflects a concerted and controlled activation of transcription and translation<br/>following the exit of cells from the cell cycle. Here we show that myogenic differentiation is associated with<br/>increased rates of translation, the up-regulation of both 4E-BP1 mRNA and protein levels and enhanced levels<br/>of eIF4E/4E-BP1 complex. Paradoxically, treatment of C2C12 myoblasts with an inhibitor of mTOR signalling<br/>(RAD001) which inhibits translation, promotes the hyperphosphorylation of 4E-BP1 on novel sites and<br/>prevents the increase in 4E-BP1 levels. In contrast, eIF4E appears to be under translational control with a<br/>significant delay between induction of mRNA and subsequent protein expression
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