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Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap

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Abstract

EUKARYOTIC cellular mRNAs have a 5' cap structure (m7 GpppX) that facilitates binding to ribosomes and is required for efficient translation1–3. A specific initiation factor, eIF-4F, mediates the function of the cap4–6 and consists of three subunits7–10, one of which, eIF-4E, binds the cap. This subunit is present in limiting amounts in the cell11–13, and is thought to be regulated by phosphorylation12–16: decreased phosphorylation of eIF-4E following various treatments correlates with a decrease in cellular translation rate. These observations suggest that eIF-4E lies on the mitogenic signal transduction pathway, and we reasoned that overexpression of eIF-4E might profoundly affect cellular growth properties. We report here that overexpression of eIF-4E in NIH 3T3 and Rat 2 fibroblasts causes their tumorigenic transformation as determined by three criteria: formation of transformed foci on a monolayer of cells; anchorage-independent growth; and tumour formation in nude mice.

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References

  1. Shatkin, A. J. Cell 9, 645–653 (1976).

    Article  CAS  PubMed  Google Scholar 

  2. Banerjee, A. K. Microbiol. Rev. 44, 175–207 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Sonenberg, N. Prog. Nucleic Acid Res. molec. Biol. 35, 173–207 (1988).

    Article  CAS  Google Scholar 

  4. Tahara S. M., Morgan, M. A. & Shatkin A. J. J. biol. Chem. 256, 7691–7694 (1981).

    CAS  PubMed  Google Scholar 

  5. Grifo, J. et al. J. Biol. Chem. 258, 5804–5810 (1983).

    CAS  PubMed  Google Scholar 

  6. Edery, I. et al. J. Biol. Chem. 258, 11398–11403 (1983).

    CAS  PubMed  Google Scholar 

  7. Sonenberg, N., Morgan, M. A., Merrick, W. C. & Shatkin, A. J. Proc. natn. Acad. Sci. U.S.A. 75, 4843–4847 (1978).

    Article  ADS  CAS  Google Scholar 

  8. Abramson, R. D. et al. J. Biol. Chem. 262, 3826–3832 (1987).

    CAS  PubMed  Google Scholar 

  9. Ray, B. K. et al. J. Biol. Chem. 260, 7651–7658 (1985).

    CAS  PubMed  Google Scholar 

  10. Rozen, F. et al. Molec. cell. Biol. 10, 1134–1144 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hiremath, L. S., Webb, N. R. & Rhoads, R. E. J. biol. Chem. 260, 7843–7849 (1985).

    CAS  PubMed  Google Scholar 

  12. Duncan, R., Milburn, S. C. & Hershey, J. W. B. J. biol. Chem. 262, 380–388 (1987).

    CAS  PubMed  Google Scholar 

  13. Rhoads, R. E. Trends Biochem. Sci. 13, 52–56 (1988).

    Article  CAS  PubMed  Google Scholar 

  14. Bonneau, A-M. & Sonenberg, N. J. biol. Chem. 262, 11134–11139 (1987).

    CAS  PubMed  Google Scholar 

  15. Marino, M. W., Pfeffer, L. M., Guidon, P. T. Jr & Donner, D. B. Proc. natn. Acad. Sci. U.S.A. 86, 8417–8421 (1989).

    Article  ADS  CAS  Google Scholar 

  16. Morley, S. J. & Traugh, J. A. J. biol. Chem. 264, 2401–2404 (1989).

    CAS  PubMed  Google Scholar 

  17. Kirschmeier, P. T. et al. DNA 7, 219–225 (1988).

    Article  CAS  PubMed  Google Scholar 

  18. Rychlik, W., Russ, M. A. & Rhoads, R. E. J. biol. Chem. 262, 10434–10437 (1987).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  20. Freedman, V. H. & Shin, S. Cell 3, 355–359 (1974).

    Article  CAS  PubMed  Google Scholar 

  21. Amrein, K. E. & Sefton, B. M. Proc. natn. Acad. Sci. U.S.A. 85, 4247–4251 (1988).

    Article  ADS  CAS  Google Scholar 

  22. Brenner, C. et al. Molec. cell. Biol. 8, 3556–3559 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Altmann, M. & Trachsel, H. Nucleic Acids Res. 17, 5923–5931 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rao, C. D., Pech, M., Robbins, K. C. & Aaronson, S. A. Molec. cell. Biol. 8, 284–292 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Marth, J. D. et al. Nature 332, 171–173 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  26. Godeau, F., Persson, H., Grey, H. E. & Pardee, A. B. EMBO J. 5, 3571–3577 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Darveau, A., Pelletier, J. & Sonenberg, N. Proc. natn. Acad. Sci. U.S.A. 82, 2315–2319 (1985).

    Article  ADS  CAS  Google Scholar 

  28. Ratner, L., Thielan, B. & Collins, T. Nucleic Acids Res. 15, 6017–6036 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Altmann, M., Miller, P. P., Pelletier, J., Sonenberg, N. & Trachsel, H. J. biol. Chem. 264, 12145–12147 (1989).

    CAS  PubMed  Google Scholar 

  30. Zoller, M. J. & Smith, M. Nucleic Acids Res. 10, 6487–6500 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ausubel, F. M. et al. in Current Protocols in Molecular Biology (Wiley, New York, 1987).

    Google Scholar 

  32. Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning (Cold Spring Harbor, New York, 1982).

    Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, McGill University, Montreal, Quebec, H3G 1Y6, Canada

    Anthoula Lazaris-Karatzas, Kathleen S. Montine & Nahum Sonenberg

  2. McGill Cancer Centre, McGill University, Montreal, Quebec, H3G 1Y6, Canada

    Nahum Sonenberg

Authors
  1. Anthoula Lazaris-Karatzas
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  2. Kathleen S. Montine
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  3. Nahum Sonenberg
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Lazaris-Karatzas, A., Montine, K. & Sonenberg, N. Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap. Nature 345, 544–547 (1990). https://doi.org/10.1038/345544a0

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