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

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

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Freeman, D. J., Li, A. G., Wei, G., Li, H. H., Kertesz, N., Lesche, R., Whale, A. D., 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, 3(2), 117-130. https://doi.org/10.1016/S1535-6108(03)00021-7