Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1993-04

AUTHORS

Jonathan D. Oliner, Jennifer A. Pietenpol, Sam Thiagalingam, Jeno Gyuris, Kenneth W. Kinzler, Bert Vogelstein

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. More... »

PAGES

857-860

Journal

TITLE

Nature

ISSUE

6423

VOLUME

362

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/362857a0

DOI

http://dx.doi.org/10.1038/362857a0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008690526

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/8479525


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