Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function

Nature volume 371, pages 762–767 (1994)Cite this article

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

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Shatkin, A. J. Cell 40, 223–224 (1985).

    Article  CAS  Google Scholar 

  2. Merrick, W. C. Microbiol. Rev. 56, 291–315 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Sonenberg, N. Gene Expression 3, 317–323 (1993).

    CAS  PubMed  Google Scholar 

  4. Hershey, J. W. B. Rev. Biochem. 60, 717–757 (1991).

    Article  CAS  Google Scholar 

  5. Hershey, J. W. B. J. biol. Chem. 264, 20823–20826 (1989).

    CAS  PubMed  Google Scholar 

  6. Lyons, R. T., Nordeen, S. K. & Young, D. A. J. biol. Chem. 255, 6330–6334 (1980).

    CAS  PubMed  Google Scholar 

  7. Morgan, H. E. et al. J. biol. Chem. 246, 2163–2170 (1971).

    CAS  PubMed  Google Scholar 

  8. Stirwalt, W. S., Wool, I. G. & Cavicchi, P. Proc. natn. Acad. Sci. U.S.A. 57, 1885–1889 (1967).

    Article  ADS  Google Scholar 

  9. Morley, S. J. & Traugh, J. A. J. biol. Chem. 265, 10611–10616 (1990).

    CAS  PubMed  Google Scholar 

  10. Manzella, J. M., Rychlik, W., Rhoads, R. E., Hershey, J. W. B. & Blackshear, P. J. J. biol. Chem. 266, 2383–2389 (1991).

    CAS  PubMed  Google Scholar 

  11. Joshi-Barve, S., Rychlik, W. & Rhoads, R. E. J. biol. Chem. 265, 2979–2983 (1990).

    CAS  PubMed  Google Scholar 

  12. Lararis-Karatzas, A., Montine, K. S. & Sonenberg, N. Nature 345, 544–547 (1990).

    Article  ADS  Google Scholar 

  13. Belsham, G. J., Brownsey, R. W., Hughes, W. A. & Denton, R. M. Diabetologia 18, 307–312 (1980).

    Article  CAS  Google Scholar 

  14. Belsham, G. J., Brownsey, R. W. & Denton, R. M. Biochem. J. 204, 345–352 (1982).

    Article  CAS  Google Scholar 

  15. Denton, R. M., Brownsey, R. W. & Belsham, G. J. Diabetologia 21, 347–363 (1981).

    Article  CAS  Google Scholar 

  16. Avruch, J. et al. in Molecular Basis of Insulin Action (ed. Czech, M. P.) 67–94 (Plenum, New York, 1985).

    Google Scholar 

  17. Haystead, T. A. J. et al. J. biol. Chem. 269, 23185–23191 (1994).

    CAS  PubMed  Google Scholar 

  18. Hu, C., Pang, S., Kong, X., Velleca, M. & Lawrence, J. C. Proc. natn. Acad. Sci. U.S.A. 91, 3730–3734 (1994).

    Article  ADS  CAS  Google Scholar 

  19. Blanar, M. A. & Rutter, W. J. Science 256, 1014–1018 (1992).

    Article  ADS  CAS  Google Scholar 

  20. Edery, I., Altmann, M. & Sonenberg, N. Gene 74, 517–525 (1988).

    Article  CAS  Google Scholar 

  21. Blackshear, P. J., Nemenoff, R. A. & Avruch, J. Biochem. J. 214, 11–19 (1983).

    Article  CAS  Google Scholar 

  22. Blackshear, P. J. et al. J. biol. Chem. 260, 13304–13315 (1985).

    CAS  PubMed  Google Scholar 

  23. Jackson, R. J., Howell, M. T. & Kaminski, A. Trends biochem. Sci. 15, 477–483 (1990).

    Article  Google Scholar 

  24. Fuerst, T. R., Niles, E. G., Studier, F. W. & Moss, B. Proc. natn. Acad. Sci. U.S.A. 83, 8122–8126 (1986).

    Article  ADS  CAS  Google Scholar 

  25. Belsham, G. J. & Brangwyn, J. K. J. Virol. 64, 5389–5395 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Gallie, D. R. & Traugh, J. A. J. biol. Chem. 269, 7174–7179 (1994).

    CAS  PubMed  Google Scholar 

  27. Rosenwald, I. B., Lazaris-Karatzas, A., Sonenberg, N. & Schmidt, E. V. Molec. cell. Biol. 13, 7358–7363 (1993).

    Article  CAS  Google Scholar 

  28. Shantz, L. M. & Pegg, A. E. Cancer Res. 54, 2313–2316 (1994).

    CAS  PubMed  Google Scholar 

  29. Hattori, M. & Sakaki, Y. Analyt. Biochem. 152, 232–238 (1986).

    Article  CAS  Google Scholar 

  30. Methot, N., Pause, A., Hershey, J. W. B. & Sonenberg, N. Molec. cell. Biol. 14, 2307–2316 (1994).

    Article  CAS  Google Scholar 

  31. Pelletier, J. & Sonenberg, N. Cell 40, 515–526 (1985).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Arnim Pause

    Present address: CBMB, NICHD, NIH, Bethesda, Maryland, 20892, USA

Authors and Affiliations

  1. Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Drummond Street, Montréal, Québec, H3G 1Y6, Canada

    Arnim Pause, Graham J. Belsham, Anne-Claude Gingras, Olivier Donzé & Nahum Sonenberg

  2. BBSRC Institute for Animal Health, Pirbright, Woking, Surrey, GU24 ONF, UK

    Graham J. Belsham

  3. Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri, 63110, USA

    Tai-An Lin & John C. Lawrence Jr

Authors
  1. Arnim Pause
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Graham J. Belsham
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anne-Claude Gingras
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Olivier Donzé
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tai-An Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John C. Lawrence Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nahum Sonenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints 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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/371762a0

This article is cited by

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.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing