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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

Inhibition of mammalian target of rapamycin (mTOR) signalling in C2C12 myoblasts prevents myogenic differentiation without affecting the hyperphosphorylation of 4E-BP1
Inhibition of mammalian target of rapamycin (mTOR) signalling in C2C12 myoblasts prevents myogenic differentiation without affecting the hyperphosphorylation of 4E-BP1
Current 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.
initiation factor, C2C12, translation, myoblasts, 4E-BP1, signaling
0898-6568
1504-1512
Willett, Mark
dfa36c04-719a-4884-87cd-2ae13a3d2b67
Cowan, Joanne L.
a34fc26a-e7a3-435f-85c8-4f196b1c8d63
Vlasak, Markete
9bb9fec4-2d64-42b9-84e7-f92be380d5b5
Coldwell, Mark J.
a3432799-ed45-4948-9f7a-2a284d3ec65c
Morley, Simon J.
059a6269-c9e5-4165-8498-238153537ceb
Willett, Mark
dfa36c04-719a-4884-87cd-2ae13a3d2b67
Cowan, Joanne L.
a34fc26a-e7a3-435f-85c8-4f196b1c8d63
Vlasak, Markete
9bb9fec4-2d64-42b9-84e7-f92be380d5b5
Coldwell, Mark J.
a3432799-ed45-4948-9f7a-2a284d3ec65c
Morley, Simon J.
059a6269-c9e5-4165-8498-238153537ceb

Willett, Mark, Cowan, Joanne L., Vlasak, Markete, Coldwell, Mark J. and Morley, Simon J. (2009) Inhibition of mammalian target of rapamycin (mTOR) signalling in C2C12 myoblasts prevents myogenic differentiation without affecting the hyperphosphorylation of 4E-BP1. Cellular Signalling, 21 (10), 1504-1512. (doi:10.1016/j.cellsig.2009.05.009). (PMID:19481146)

Record type: Article

Abstract

Current 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.

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More information

Published date: October 2009
Keywords: initiation factor, C2C12, translation, myoblasts, 4E-BP1, signaling
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 142007
URI: http://eprints.soton.ac.uk/id/eprint/142007
ISSN: 0898-6568
PURE UUID: 30331076-051b-4a43-80e3-801ed2191129
ORCID for Mark J. Coldwell: ORCID iD orcid.org/0000-0002-6243-3886

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Date deposited: 30 Mar 2010 13:19
Last modified: 14 Mar 2024 00:38

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Contributors

Author: Mark Willett
Author: Joanne L. Cowan
Author: Markete Vlasak
Author: Mark J. Coldwell ORCID iD
Author: Simon J. Morley

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