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:

Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein

Abstract

THE MDM2 proto-oncogene is found amplified in a variety of tumours1. The oncogenic capacity of the MDM2 protein is attributed to its ability to bind the p53 tumour-suppressor protein and mask its transcriptional activation potential2,3. Here we show that MDM2 makes a functional contact with two cooperating transcription factors, E2F1 and DPI (refs 4, 5), which are involved in S-phase progression6. MDM2 contacts the activation domain of E2F1 using residues conserved in the activation domain of p53. However, in contrast to its repression of p53 activity, MDM2 stimulates the activation capacity of E2F1/DP1. These results indicate that MDM2 not only releases a proliferative block by silencing the tumour suppressor p53, it also positively augments proliferation by stimulating the S-phase inducing transcription factors E2F1/DPI.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Oliner, J. D., Kinzler, K. W., Meltzer, P. S., George, D. L. & Vogelstein, B. Nature 358, 80–83 (1992).

    Article  ADS  CAS  Google Scholar 

  2. Oliner, J. D. et al. Nature 362, 857–860 (1993).

    Article  ADS  CAS  Google Scholar 

  3. Momand, J., Zambetti, G. P., Olson, D. C., George, D. & Levine, A. J. Cell 69, 1237–1245 (1992).

    Article  CAS  Google Scholar 

  4. Bandara, R. L., Buck, V. M., Zamanian, M., Johnston, L. H. & La Thangue, N. B. EMBO J. 12, 4317–4324 (1993).

    Article  CAS  Google Scholar 

  5. Helin, K. et al. Genes Dev. 7, 1850–1861 (1993).

    Article  CAS  Google Scholar 

  6. Johnson, D. G., Schwarz, J. K., Cress, W. D. & Nevins, J. R. Nature 365, 349–352 (1993).

    Article  ADS  CAS  Google Scholar 

  7. Brown, D. R., Deb, S., Munoz, M. B., Subler, M. A. & Deb, S. P. Molec. cell. Biol. 13, 6849–6857 (1993).

    Article  CAS  Google Scholar 

  8. Haines, D. S., Landers, J. E., Engle, L. J. & George, D. L. Molec. cell. Biol. 14, 1171–1178 (1994).

    Article  CAS  Google Scholar 

  9. Picksley, S. M., Vojtesek, B., Sparks, A. & Lane, D. P. Oncogene 9, 2523–2529 (1994).

    CAS  PubMed  Google Scholar 

  10. Hagemeier, C., Cook, A. & Kouzarides, T. Nucleic Acids Res. 21, 4998–5004 (1993).

    Article  CAS  Google Scholar 

  11. Seto, E. et al. Proc. natn. Acad. Sci. U.S.A. 89, 12028–12032 (1992).

    Article  ADS  CAS  Google Scholar 

  12. Helin, K., Harlow, E. & Fattay, A. Molec. cell. Biol. 13, 6501–6508 (1993).

    Article  CAS  Google Scholar 

  13. Flemington, E. K., Spek, S. H. & Kaelin, W. G. Proc. natn. Acad. Sci. U.S.A. 90, 6914–6918 (1993).

    Article  ADS  CAS  Google Scholar 

  14. Kaelin, W. G. et al. Cell 70, 351–364 (1992).

    Article  CAS  Google Scholar 

  15. Zamanian, M. & La Thangue, N. B. EMBO J. 11, 2603–2610 (1992).

    Article  CAS  Google Scholar 

  16. Baker, S. J., Morkowitz, S., Fearon, E. R., Willson, J. K. & Vogelstein, B. Science 249, 912–915 (1990).

    Article  ADS  CAS  Google Scholar 

  17. Kern, S. E. et al. Science 256, 827–830 (1992).

    Article  ADS  CAS  Google Scholar 

  18. Helin, K. et al. Cell 70, 337–350 (1992).

    Article  CAS  Google Scholar 

  19. Liu, X., Miller, C. W., Koeffler, P. H. & Berk, A. J. Molec. cell. Biol. 13, 3291–3300 (1993).

    Article  CAS  Google Scholar 

  20. Barak, Y., Gottlieb, E., Juren-Gerhon, T. & Oren, M. Genes Dev. 8, 1739–1749 (1994).

    Article  CAS  Google Scholar 

  21. Bandara, L. R. et al. EMBO J. 13, 3104–3114 (1994).

    Article  CAS  Google Scholar 

  22. Lillie, J. W. & Green, M. R. Nature 338, 39–44 (1989).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martin, K., Trouche, D., Hagemeier, C. et al. Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein. Nature 375, 691–694 (1995). https://doi.org/10.1038/375691a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/375691a0

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