Letter | Published:

Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53

Nature volume 362, pages 857860 (29 April 1993) | Download Citation

Subjects

Abstract

THE tumour-suppressor gene p53 is inactivated in most human malignancies1 either by missense mutations1 or by binding to oncogenic proteins2–4. In human soft tissue sarcomas, inactivation apparently results from MDM2 gene amplification4. MDM2 is an oncogene product5,6 that may function by binding to p53 and inhibiting its ability to activate transcription3. Here we show that, when expressed in Saccharomyces cerevisiae, human MDM2 inhibits human p53's ability to stimulate transcription by binding to a region that nearly coincides with the p53 acidic activation domain. The isolated p53 activation domain fused to another DNA-binding protein is also inactivated by MDM2, confirming that MDM2 can inhibit p53 function by concealing the activation domain of p53 from the cellular transcription machinery.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , , & Science 253, 49–53 (1991).

  2. 2.

    , , , & Cell 63, 1129–1136 (1990).

  3. 3.

    , , & Cell 69, 1237–1245 (1992).

  4. 4.

    , , , & Nature 358, 80–83 (1992).

  5. 5.

    , & EMBO J. 10, 1565–1569 (1991).

  6. 6.

    Molec. cell. Biol. 13, 301–306 (1993).

  7. 7.

    & Cell 70, 523–526 (1992).

  8. 8.

    et al. Science 256, 827–830 (1992).

  9. 9.

    , , , & Molec. cell. Biol. 10, 2840–2847 (1990).

  10. 10.

    & Science 249, 1046–1049 (1990).

  11. 11.

    , & Science 249, 1049–1051 (1990).

  12. 12.

    , , & EMBO J. 11, 1383–1390 (1992).

  13. 13.

    , , , & Proc. Am. Assoc. Cancer Res. 33, 386 (1992).

  14. 14.

    , , & Molec. Carcinogen. 5, 102–106 (1992).

  15. 15.

    et al. Oncogene 7, 1513–1523 (1992).

  16. 16.

    , , & Proc. natn. Acad. Sci. U.S.A. (in the press).

  17. 17.

    & Cell 65, 765–774 (1991).

  18. 18.

    & Science 256, 1333–1335 (1992).

  19. 19.

    & Cell 50, 137–142 (1987).

  20. 20.

    , , & Molec. cell. Biol. 12, 1357–1365 (1992).

  21. 21.

    , , , & Nature 350, 250–252 (1991).

  22. 22.

    et al. Molec. cell. Biol. 11, 4809–4821 (1991).

  23. 23.

    , & Cell 68, 597–612 (1992).

  24. 24.

    & Nucleic Acids Res. 17, 3645–3653 (1989).

  25. 25.

    & Molec. cell. Biol. 12, 3006–3014 (1992).

  26. 26.

    , & Nature 340, 245–246 (1989).

  27. 27.

    et al. J. biol. Chem. 258, 13258–13261 (1983).

Download references

Author information

Affiliations

  1. The Johns Hopkins Oncology Centre, 424 North Bond Street, Baltimore, Maryland 21231, USA

    • Jonathan D. Oliner
    • , Jennifer A. Pietenpol
    • , Sam Thiagalingam
    • , Kenneth W. Kinzler
    •  & Bert Vogelstein
  2. Program in Human Genetics, The Johns Hopkins University, School of Medicine, Baltimore, Maryland 21231, USA

    • Jonathan D. Oliner
    •  & Bert Vogelstein
  3. Department of Genetics, Harvard Medical School, and Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA

    • Jeno Gyuris
  4. To whom correspondence should be addressed.

    • Bert Vogelstein

Authors

  1. Search for Jonathan D. Oliner in:

  2. Search for Jennifer A. Pietenpol in:

  3. Search for Sam Thiagalingam in:

  4. Search for Jeno Gyuris in:

  5. Search for Kenneth W. Kinzler in:

  6. Search for Bert Vogelstein in:

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/362857a0

Further reading

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.