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Differing effects of rapamycin and mTOR kinase inhibitors on protein synthesis.

Huo, Y, Iadevaia, V and Proud, CG (2011) Differing effects of rapamycin and mTOR kinase inhibitors on protein synthesis. Biochem Soc Trans, 39 (2). pp. 446-450.

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Abstract

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.

Item Type: Article
Authors :
NameEmailORCID
Huo, YUNSPECIFIEDUNSPECIFIED
Iadevaia, Vv.iadevaia@surrey.ac.ukUNSPECIFIED
Proud, CGUNSPECIFIEDUNSPECIFIED
Date : April 2011
Identification Number : https://doi.org/10.1042/BST0390446
Uncontrolled Keywords : Animals, Humans, Isotope Labeling, Models, Biological, Protein Biosynthesis, Protein Kinase Inhibitors, Sirolimus, TOR Serine-Threonine Kinases
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:28
Last Modified : 17 May 2017 14:49
URI: http://epubs.surrey.ac.uk/id/eprint/827939

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