Regulation of PTEN transcription by p53

V. Stambolic, D. MacPherson, D. Sas, Y. Lin, B. Snow, Y. Jang, S. Benchimol, T. W. Mak

Research output: Contribution to journalArticlepeer-review

696 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)317-325
Number of pages9
JournalMolecular Cell
Volume8
Issue number2
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
We thank Greg Arnold for help with sequence analysis, Angie Nelson for oligonucleotide synthesis, Ming-Sound Tsao for HBEC cells, Ayeda Ayed and Cheryl Arrowsmith for bacteria expressing recombinant p53, Joan Mangion for protein purification, and Malte Peters, Scott Pownall, Wen-Chen Yeh, and Mary Saunders for critical reading of the manuscript. V.S. is a recipient of a post-doctoral fellowship from the Cancer Research Institute, New York.

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