Regulation of PTEN transcription by p53.

Publication Type:

Journal Article

Source:

Molecular cell, Volume 8, Issue 2, p.317-25 (2001)

Keywords:

Animals, APOPTOSIS, Cell Line, Embryo, Mammalian, Fibroblasts, Gamma Rays, Genes, p53, Genes, Reporter, Genes, Tumor Suppressor, Humans, Immunoblotting, MICE, Molecular Sequence Data, Phosphoric Monoester Hydrolases, Promoter Regions, Genetic, PTEN Phosphohydrolase, Temperature, Transcription, Genetic, TRANSCRIPTIONAL ACTIVATION, Transfection, Tumor Suppressor Protein p53, Tumor Suppressor Proteins

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.