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.
Original language | English (US) |
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Pages (from-to) | 117-130 |
Number of pages | 14 |
Journal | Cancer Cell |
Volume | 3 |
Issue number | 2 |
DOIs | |
State | Published - Jan 1 2003 |
ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research