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Inhibition of mammalian target of rapamycin (mTOR) signalling in C2C12 myoblasts prevents myogenic differentiation without affecting the hyperphosphorylation of 4E-BP1
journal contribution
posted on 2023-06-08, 07:12 authored by Mark Willett, Joanne L Cowan, Markete Vlasak, Mark J Coldwell, Simon MorleyCurrent accepted models suggest that hypophosphorylated 4E-binding protein (4E-BP1) binds to initiation factor 4E (eIF4E) to inhibit cap-dependent translation, a process readily reversed by its phosphorylation following activation of mammalian target of rapamycin (mTORC1) signalling. Myogenic differentiation in the C2C12 myoblast model system reflects a concerted and controlled activation of transcription and translation following the exit of cells from the cell cycle. Here we show that myogenic differentiation is associated with increased rates of translation, the up-regulation of both 4E-BP1 mRNA and protein levels and enhanced levels of eIF4E/4E-BP1 complex. Paradoxically, treatment of C2C12 myoblasts with an inhibitor of mTOR signalling (RAD001) which inhibits translation, promotes the hyperphosphorylation of 4E-BP1 on novel sites and prevents the increase in 4E-BP1 levels. In contrast, eIF4E appears to be under translational control with a significant delay between induction of mRNA and subsequent protein expression.
History
Publication status
- Published
Journal
Cellular SignallingISSN
0898-6568Publisher
ElsevierExternal DOI
Issue
10Volume
21Page range
1504-1512Pages
9.0Department affiliated with
- Biochemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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