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Mol Cell. 2001 Aug;8(2):317-25.

Regulation of PTEN transcription by p53.

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  • 1Amgen Research Institute and, Ontario Cancer Institute, 620 University Avenue, Ontario, Toronto, Canada.

Abstract

PTEN tumor suppressor is frequently mutated in human cancers and is a negative regulator of PI3'K/PKB/Akt-dependent cellular survival. Investigation of the human genomic PTEN locus revealed a p53 binding element directly upstream of the PTEN gene. Deletion and mutation analyses showed that this element is necessary for inducible transactivation of PTEN by p53. A p53-independent element controlling constitutive expression of PTEN was also identified. In contrast to p53 mutant cell lines, induction of p53 in primary and tumor cell lines with wild-type p53 increased PTEN mRNA levels. PTEN was required for p53-mediated apoptosis in immortalized mouse embryonic fibroblasts. Our results reveal a unique role for p53 in regulation of cellular survival and an interesting connection in tumor suppressor signaling.

PMID:
11545734
[PubMed - indexed for MEDLINE]
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