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Distinct Repression of Translation by Wortmannin and Rapamycin
Abstract
The role of phosphatidylinositol 3‐kinase and FK506‐binding protein · rapamycin‐associated protein (FRAP) in translational control has been examined by treating RD‐rhabdomyosarcoma cells with wortmannin and rapamycin and studying the effects on cell‐growth, translation initiation, and protein synthesis. Whereas wortmannin and rapamycin exhibit subtle effects on global translation, examination of individual mRNAs in sucrose gradients and of individual proteins in two‐dimensional polyacrylamide gels reveals that wortmannin and rapamycin exhibit distinct effects on the translation of individual mRNAs. Wortmannin represses the synthesis of a third of cellular proteins, whereas rapamycin affects a subset of these proteins. Since ribosomal protein S6 was rapidly dephosphorylated following wortmannin and rapamycin treatment, and the phosphorylation status of the eukaryotic initiation factor 4E was unchanged, our data imply that the p70 signalling pathway has at least one branch‐point upstream of FRAP leading to an additional route of translational control.
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“Further, neither mTOR inhibition by rapamycin or deletion of S6K1 significantly slows protein translation in mice or cells 52–54.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [54]
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Sorted by citations
Thoreen, C. C., Kang, S. A., Chang, J. W., Liu, Q., Zhang, J., Gao, Y., Reichling, L. J., Sim, T., Sabatini, D. M., & Gray, N. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900301200 · Cited by 1,803
Regulation of translation initiation by FRAP/mTOR
Gingras, A.-C., Raught, B., & Sonenberg, N. (2001) · Genes & Development · doi:10.1101/gad.887201 · Cited by 1,545
Dowling, R. J. O., Zakikhani, M., Fantus, I. G., Pollak, M., & Sonenberg, N. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2310 · Cited by 933
Rapalogs and mTOR inhibitors as anti-aging therapeutics
Lamming, D. W., Ye, L., Sabatini, D. M., & Baur, J. A. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64099 · Cited by 531
Targeting the biology of aging with mTOR inhibitors
Mannick, J. B., & Lamming, D. W. (2023) · Nature Aging · doi:10.1038/s43587-023-00416-y · Cited by 372
Drake, J. C., Peelor, F. F., Biela, L. M., Watkins, M. K., Miller, R. A., Hamilton, K. L., & Miller, B. F. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt047 · Cited by 87
Metadata
- Authors
- Pedersen, S., Celis, J. E., Nielsen, J., Christiansen, J., & Nielsen, F. C.
- Venue
- European Journal of Biochemistry
- Publisher
- Wiley
- Published
- 1997-07
- Volume
- 247
- Issue
- 1
- Pages
- 449-456
- ISSN
- 0014-2956
- 1432-1033
- Cited by
- 36
- References
- 0
- Language
- en
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