Cancer Cell
Volume 3, Issue 2, February 2003, Pages 117-130
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Article
PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms

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Abstract

We show in this study that PTEN regulates p53 protein levels and transcriptional activity through both phosphatase-dependent and -independent mechanisms. The onset of tumor development in p53+/−;Pten+/− mice is similar to p53−/− animals, and p53 protein levels are dramatically reduced in Pten−/− cells and tissues. Reintroducing wild-type or phosphatase-dead PTEN mutants leads to a significant increase in p53 stability. PTEN also physically associates with endogenous p53. Finally, PTEN regulates the transcriptional activity of p53 by modulating its DNA binding activity. This study provides a novel mechanism by which the loss of PTEN can functionally control “two” hits in the course of tumor development by concurrently modulating p53 activity.

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These two authors contributed equally.

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Present address: Epigenomics AG, Kastanienallee 24, 10435 Berlin, Germany.