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.

  • Letter
  • Published:

The cellular oncogene p53 can be activated by mutagenesis

Abstract

p53 is a cellular phosphoprotein of short half-life (t1/2;) which is present at elevated levels in cells transformed by various stimuli including viruses, chemicals and radiation1–5. p53 forms specific stable complexes with simian virus 40 (SV40) large-T itntigen and an adenovirus Elb protein of relative molecular mass (Mr) 57,000 (refs 4–7). A number of reports have associated p53 with cell proliferation8–11, and p53 complementary DNA expression constructs immortalize primary cells in vitro12 and render them sensitive to transformation by an activated ras oncogene12–14. We have examined the biological properties of a set of p53 expression constructs, and report here that cellular immortalization by a wild-type p53 cDNA gene is conditional upon the promoter/enhancer construction used, but that p53 can extend cellular lifespan by a second distinct mechanism involving rearrangements of the coding sequence which give rise to stable protein products. Cells immortalized by one of these mutants are refractory to subsequent transformation by a ras oncogene, indicating that cellular immortalization and ras cooperation are separate activities.

This is a preview of subscription content, access via your institution

Access options

Buy this article

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

Similar content being viewed by others

References

  1. DeLeo, A. B. et al. Proc. natn. Acad. Sci. U.S.A. 76, 2420–2424 (1979).

    Article  ADS  CAS  Google Scholar 

  2. Rotter, V. Proc. natn. Acad. Sci. U.S.A. 90, 2613–2617 (1983).

    Article  ADS  Google Scholar 

  3. Rotter, V., Boss, M. A. & Baltimore, D. J. Virol. 38, 336–346 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Lane, D. P. & Crawford, L. V. Nature 278, 261–263 (1979).

    Article  ADS  CAS  Google Scholar 

  5. Linzer, D. I. H. & Levine, A. J. Cell 17, 43–52 (1979).

    Article  CAS  Google Scholar 

  6. Oren, M., Maltzman, W. & Levine, A. J. Molec. cell. Biol. 1, 101–110 (1981).

    Article  CAS  Google Scholar 

  7. McCormick, F. & Harlow, E. J. Virol. 34, 213–224 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Sarnow, P., Ho, Y. S., Williams, J. & Levine, A. J. Cell 28, 387–394 (1982).

    Article  CAS  Google Scholar 

  9. Milner, J. & McCormick, F. Cell Biol. int. Rep. 4, 663–667 (1980).

    Article  CAS  Google Scholar 

  10. Milner, J. & Milner, S. Virology 112, 785–788 (1981).

    Article  CAS  Google Scholar 

  11. Mercer, W. E., Nelson, D., DeLeo, A. B., Old, L. J. & Baserga, R. Proc. natn. Acad. Sci. U.S.A. 79, 6309–6312 (1982).

    Article  ADS  CAS  Google Scholar 

  12. Jenkins, J. R., Rudge, K. & Currie, G. A. Nature 312, 651–654 (1984).

    Article  ADS  CAS  Google Scholar 

  13. Eliyahu, D., Raz, A., Gruss, P., Givol, D. & Oren, M. Nature 312, 646–649 (1984).

    Article  ADS  CAS  Google Scholar 

  14. Parada, L. F., Land, H., Weinberg, R. A., Wolf, D. & Rotter, V. Nature 312, 649–651 (1984).

    Article  ADS  CAS  Google Scholar 

  15. Kalderon, D., Richardson, W. D., Markham, A. F. & Smith, A. E. Nature 311, 33–38 (1984).

    Article  ADS  CAS  Google Scholar 

  16. Newbold, R. F., Overell, R. W. & Connell, J. R. Nature 299, 633–635 (1982).

    Article  ADS  CAS  Google Scholar 

  17. Ruley, H. E. Nature 304, 602–606 (1983).

    Article  ADS  CAS  Google Scholar 

  18. Land, H., Parada, L. F. & Weinberg, R. A. Nature 304, 596–602 (1983).

    Article  ADS  CAS  Google Scholar 

  19. Klein, G. Cancer Res. 19, 343–358 (1959).

    CAS  PubMed  Google Scholar 

  20. Newbold, R. F. & Overell, R. W. Nature 304, 648 (1983).

    Article  ADS  CAS  Google Scholar 

  21. Jenkins, J. R., Rudge, K., Redmond, S. & Wade-Evans, A. Nucleic Acids Res. 12, 5609–5626 (1984).

    Article  CAS  Google Scholar 

  22. Harlow, E., Crawford, L. V., Pim, D. C. & Williamson, N. M. J. Virol. 34, 861–869 (1981).

    Google Scholar 

  23. Coffman, R. L. & Weissman, I. L. J. exp. Med. 153, 269–279 (1981).

    Article  CAS  Google Scholar 

  24. Laemmli, U. K. Nature 277, 680–685 (1970).

    Article  ADS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jenkins, J., Rudge, K., Chumakov, P. et al. The cellular oncogene p53 can be activated by mutagenesis. Nature 317, 816–818 (1985). https://doi.org/10.1038/317816a0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/317816a0

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

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