Abstract
The cloning is described of two related human complementary DNAs encoding polypeptides that interact specifically with the translation initiation factor elF-4E, which binds to the messenger RNA 5'-cap structure. Interaction of these proteins with elF-4E inhibits translation but treatment of cells with insulin causes one of them to become hyperphosphorylated and dissociate from elF-4E, thereby relieving the translational inhibition. The action of this new regulator of protein synthesis is therefore modulated by insulin, which acts to stimulate the overall rate of translation and promote cell growth.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Shatkin, A. J. Cell 40, 223–224 (1985).
Merrick, W. C. Microbiol. Rev. 56, 291–315 (1992).
Sonenberg, N. Gene Expression 3, 317–323 (1993).
Hershey, J. W. B. Rev. Biochem. 60, 717–757 (1991).
Hershey, J. W. B. J. biol. Chem. 264, 20823–20826 (1989).
Lyons, R. T., Nordeen, S. K. & Young, D. A. J. biol. Chem. 255, 6330–6334 (1980).
Morgan, H. E. et al. J. biol. Chem. 246, 2163–2170 (1971).
Stirwalt, W. S., Wool, I. G. & Cavicchi, P. Proc. natn. Acad. Sci. U.S.A. 57, 1885–1889 (1967).
Morley, S. J. & Traugh, J. A. J. biol. Chem. 265, 10611–10616 (1990).
Manzella, J. M., Rychlik, W., Rhoads, R. E., Hershey, J. W. B. & Blackshear, P. J. J. biol. Chem. 266, 2383–2389 (1991).
Joshi-Barve, S., Rychlik, W. & Rhoads, R. E. J. biol. Chem. 265, 2979–2983 (1990).
Lararis-Karatzas, A., Montine, K. S. & Sonenberg, N. Nature 345, 544–547 (1990).
Belsham, G. J., Brownsey, R. W., Hughes, W. A. & Denton, R. M. Diabetologia 18, 307–312 (1980).
Belsham, G. J., Brownsey, R. W. & Denton, R. M. Biochem. J. 204, 345–352 (1982).
Denton, R. M., Brownsey, R. W. & Belsham, G. J. Diabetologia 21, 347–363 (1981).
Avruch, J. et al. in Molecular Basis of Insulin Action (ed. Czech, M. P.) 67–94 (Plenum, New York, 1985).
Haystead, T. A. J. et al. J. biol. Chem. 269, 23185–23191 (1994).
Hu, C., Pang, S., Kong, X., Velleca, M. & Lawrence, J. C. Proc. natn. Acad. Sci. U.S.A. 91, 3730–3734 (1994).
Blanar, M. A. & Rutter, W. J. Science 256, 1014–1018 (1992).
Edery, I., Altmann, M. & Sonenberg, N. Gene 74, 517–525 (1988).
Blackshear, P. J., Nemenoff, R. A. & Avruch, J. Biochem. J. 214, 11–19 (1983).
Blackshear, P. J. et al. J. biol. Chem. 260, 13304–13315 (1985).
Jackson, R. J., Howell, M. T. & Kaminski, A. Trends biochem. Sci. 15, 477–483 (1990).
Fuerst, T. R., Niles, E. G., Studier, F. W. & Moss, B. Proc. natn. Acad. Sci. U.S.A. 83, 8122–8126 (1986).
Belsham, G. J. & Brangwyn, J. K. J. Virol. 64, 5389–5395 (1990).
Gallie, D. R. & Traugh, J. A. J. biol. Chem. 269, 7174–7179 (1994).
Rosenwald, I. B., Lazaris-Karatzas, A., Sonenberg, N. & Schmidt, E. V. Molec. cell. Biol. 13, 7358–7363 (1993).
Shantz, L. M. & Pegg, A. E. Cancer Res. 54, 2313–2316 (1994).
Hattori, M. & Sakaki, Y. Analyt. Biochem. 152, 232–238 (1986).
Methot, N., Pause, A., Hershey, J. W. B. & Sonenberg, N. Molec. cell. Biol. 14, 2307–2316 (1994).
Pelletier, J. & Sonenberg, N. Cell 40, 515–526 (1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pause, A., Belsham, G., Gingras, AC. et al. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function. Nature 371, 762–767 (1994). https://doi.org/10.1038/371762a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/371762a0
This article is cited by
-
Foxo3a tempers excessive glutaminolysis in activated T cells to prevent fatal gut inflammation in the murine IL-10−/− model of colitis
Cell Death & Differentiation (2022)
-
mTOR-FABP4 signal is activated in brain arteriovenous malformations in humans
Journal of Molecular Medicine (2022)
-
Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin
BMC Cancer (2021)
-
Huntington’s Chorea—a Rare Neurodegenerative Autosomal Dominant Disease: Insight into Molecular Genetics, Prognosis and Diagnosis
Applied Biochemistry and Biotechnology (2021)
-
Branched-chain α-ketoacids are preferentially reaminated and activate protein synthesis in the heart
Nature Communications (2021)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.