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Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53

Nature volume 362, pages 857–860 (1993)Cite this article

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.

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Author notes

  1. Bert Vogelstein: To whom correspondence should be addressed.

Authors and 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

Authors
  1. Jonathan D. Oliner
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  2. Jennifer A. Pietenpol
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  3. Sam Thiagalingam
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  4. Jeno Gyuris
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  5. Kenneth W. Kinzler
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  6. Bert Vogelstein
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Oliner, J., Pietenpol, J., Thiagalingam, S. et al. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature 362, 857–860 (1993). https://doi.org/10.1038/362857a0

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