PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms

Daniel J. Freeman; Andrew G. Li; Gang Wei; Heng Hong Li; Nathalie Kertesz; Ralf Lesche; Andrew D. Whale; Hilda Martinez-Diaz; Nora Rozengurt; Robert Cardiff; Xuan Liu; Hong Wu

doi:10.1016/S1535-6108(03)00021-7

PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms

Daniel J. Freeman, Andrew G. Li, Gang Wei, Heng Hong Li, Nathalie Kertesz, Ralf Lesche, Andrew D. Whale, Hilda Martinez-Diaz, Nora Rozengurt, Robert Cardiff, Xuan Liu, Hong Wu

School of Veterinary Medicine

Research output: Contribution to journal › Article › peer-review

394 Scopus citations

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)
Pages (from-to)	117-130
Number of pages	14
Journal	Cancer Cell
Volume	3
Issue number	2
DOIs	https://doi.org/10.1016/S1535-6108(03)00021-7
State	Published - Jan 1 2003

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms. / Freeman, Daniel J.; Li, Andrew G.; Wei, Gang; Li, Heng Hong; Kertesz, Nathalie; Lesche, Ralf; Whale, Andrew D.; Martinez-Diaz, Hilda; Rozengurt, Nora; Cardiff, Robert; Liu, Xuan; Wu, Hong.

In: Cancer Cell, Vol. 3, No. 2, 01.01.2003, p. 117-130.

Research output: Contribution to journal › Article › peer-review

Freeman, Daniel J. ; Li, Andrew G. ; Wei, Gang ; Li, Heng Hong ; Kertesz, Nathalie ; Lesche, Ralf ; Whale, Andrew D. ; Martinez-Diaz, Hilda ; Rozengurt, Nora ; Cardiff, Robert ; Liu, Xuan ; Wu, Hong. / PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms. In: Cancer Cell. 2003 ; Vol. 3, No. 2. pp. 117-130.

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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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AU - Freeman, Daniel J.

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AU - Li, Heng Hong

AU - Kertesz, Nathalie

AU - Lesche, Ralf

AU - Whale, Andrew D.

AU - Martinez-Diaz, Hilda

AU - Rozengurt, Nora

AU - Cardiff, Robert

AU - Liu, Xuan

AU - Wu, Hong

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AB - 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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PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms

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