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

Research output: Contribution to journalArticle

368 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)117-130
Number of pages14
JournalCancer Cell
Volume3
Issue number2
DOIs
StatePublished - Jan 1 2003

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Tumor Suppressor Protein p53
Phosphoric Monoester Hydrolases
PTEN Phosphohydrolase
Neoplasms
Proteins
DNA

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

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 journalArticle

Freeman, DJ, Li, AG, Wei, G, Li, HH, Kertesz, N, Lesche, R, Whale, AD, Martinez-Diaz, H, Rozengurt, N, Cardiff, R, Liu, X & Wu, H 2003, 'PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms', Cancer Cell, vol. 3, no. 2, pp. 117-130. https://doi.org/10.1016/S1535-6108(03)00021-7
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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