mTOR (mammalian target of rapamycin) forms two distinct types of complex, mTORC (mTOR complex) 1 and 2. Rapamycin inhibits some of the functions of mTORC1, whereas newly developed mTOR kinase inhibitors interfere with the actions of both types of complex. We have explored the effects of rapamycin and mTOR kinase inhibitors on general protein synthesis and, using a new stable isotope-labelling method, the synthesis of specific proteins. In HeLa cells, rapamycin only had a modest effect on total protein synthesis, whereas mTOR kinase inhibitors decreased protein synthesis by approx. 30%. This does not seem to be due to the ability of mTOR kinase inhibitors to block the binding of eIFs (eukaryotic initiation factors) eIF4G and eIF4E. Analysis of the effects of the inhibitors on the synthesis of specific proteins showed a spectrum of behaviours. As expected, synthesis of proteins encoded by mRNAs that contain a 5′-TOP (5′-terminal oligopyrimidine tract) was impaired by rapamycin, but more strongly by mTOR kinase inhibition. Several proteins not known to be encoded by 5′-TOP mRNAs also showed similar behaviour. Synthesis of proteins encoded by ‘non-TOP’ mRNAs was less inhibited by mTOR kinase inhibitors and especially by rapamycin. The implications of our findings are discussed.
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April 2011
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Conference Article|
March 22 2011
Differing effects of rapamycin and mTOR kinase inhibitors on protein synthesis
Yilin Huo;
Yilin Huo
1School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
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Valentina Iadevaia;
Valentina Iadevaia
1School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
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Christopher G. Proud
Christopher G. Proud
1
1School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
October 25 2010
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (2): 446–450.
Article history
Received:
October 25 2010
Citation
Yilin Huo, Valentina Iadevaia, Christopher G. Proud; Differing effects of rapamycin and mTOR kinase inhibitors on protein synthesis. Biochem Soc Trans 1 April 2011; 39 (2): 446–450. doi: https://doi.org/10.1042/BST0390446
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