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Differing effects of rapamycin and mTOR kinase inhibitors on protein synthesis

Differing effects of rapamycin and mTOR kinase inhibitors on protein synthesis
Differing effects of rapamycin and mTOR kinase inhibitors on protein synthesis
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.
mammalian target of rapamycin (mTOR), mRNA, pulsed stable isotope labelling of proteins with amino acids in cell culture (pSILAC), rapamycin, translation, 5?-terminal oligopyrimidine tract (5?-TOP)
0300-5127
446-450
Huo, Yilin
5ed5cc05-b575-43c0-b72b-306ee7bb1380
Iadevaia, Valentina
1124252e-5709-4a5e-8a4b-956ced0c9611
Proud, Christopher G.
59dabfc8-4b44-4be8-a17f-578a58550cb3
Huo, Yilin
5ed5cc05-b575-43c0-b72b-306ee7bb1380
Iadevaia, Valentina
1124252e-5709-4a5e-8a4b-956ced0c9611
Proud, Christopher G.
59dabfc8-4b44-4be8-a17f-578a58550cb3

Huo, Yilin, Iadevaia, Valentina and Proud, Christopher G. (2011) Differing effects of rapamycin and mTOR kinase inhibitors on protein synthesis. Biochemical Society Transactions, 39 (2), 446-450. (doi:10.1042/BST0390446). (PMID:21428917)

Record type: Article

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.

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More information

Published date: 2011
Keywords: mammalian target of rapamycin (mTOR), mRNA, pulsed stable isotope labelling of proteins with amino acids in cell culture (pSILAC), rapamycin, translation, 5?-terminal oligopyrimidine tract (5?-TOP)
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 350251
URI: http://eprints.soton.ac.uk/id/eprint/350251
ISSN: 0300-5127
PURE UUID: 4493907c-3d7f-466c-aa0f-a52c0349811b

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Date deposited: 20 Mar 2013 12:46
Last modified: 16 Jul 2019 21:40

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