Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53

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阅读量：

142

作者：

JD Oliner，JA Pietenpol，S Thiagalingam，J Gyuris，KW Kinzler，B Vogelstein

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摘要：

THE tumour-suppressor gene p53 is inactivated in most human malignancies 1 either by missense mutations 1 or by binding to oncogenic proteins 2–4 . In human soft tissue sarcomas, inactivation apparently results from MDM2 gene amplification 4 . MDM2 is an oncogene product 5,6 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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关键词：

Oncoprotein MDM2 conceals the activation domain of tumor suppressor p53, Artículo

DOI：

10.1038/362857a0

被引量：

3597

年份：

1993