PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms.
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.
Mesh Terms:
Animals, Blotting, Northern, Blotting, Western, Cell Line, Chromatin, Cyclin D1, Electrophoretic Mobility Shift Assay, Fibroblasts, Gene Expression Regulation, Genes, Tumor Suppressor, Glutathione Transferase, Humans, Immunoblotting, Mice, Mice, Knockout, Nuclear Proteins, PTEN Phosphohydrolase, Phosphoric Monoester Hydrolases, Precipitin Tests, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Transfection, Tumor Suppressor Protein p53, Tumor Suppressor Proteins
Animals, Blotting, Northern, Blotting, Western, Cell Line, Chromatin, Cyclin D1, Electrophoretic Mobility Shift Assay, Fibroblasts, Gene Expression Regulation, Genes, Tumor Suppressor, Glutathione Transferase, Humans, Immunoblotting, Mice, Mice, Knockout, Nuclear Proteins, PTEN Phosphohydrolase, Phosphoric Monoester Hydrolases, Precipitin Tests, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Transfection, Tumor Suppressor Protein p53, Tumor Suppressor Proteins
Cancer Cell
Date: Feb. 01, 2003
PubMed ID: 12620407
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