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Updated: Sep 27, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent
Daniel J Freeman1, Andrew G Li, Gang Wei
1Howard Hughes Medical Institute, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095, USA.
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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