Skip to main content

Advertisement

SpringerLink
Log in

Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

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, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

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

Author notes

  1. Christian Hagemeier

    Present address: Labor fur padiatrische Molekularbiologie, Ziegelstr. 5-9, 10117, Berlin, Germany

Authors and Affiliations

  1. Wellcome/CRC Institute, Tennis Court Road, Cambridge, CB2 1QR

    Klaus Martin, Didier Trouche, Christian Hagemeier & Tony Kouzarides

  2. Department of Pathology, University of Cambridge, Cambridge, UK

    Klaus Martin, Didier Trouche, Christian Hagemeier & Tony Kouzarides

  3. MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Troels S. Sorensen & Nicholas B. La Thangue

Authors
  1. Klaus Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Didier Trouche
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christian Hagemeier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Troels S. Sorensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nicholas B. La Thangue
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tony Kouzarides
    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

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

  • Springer Nature Limited

This article is cited by

Search

Navigation