PTEN tumor suppressor is frequently mutated in human cancers and is a negat
ive regulator of P13'K/PKB/Akt-dependent cellular survival. Investigation o
f the human genomic PTEN locus revealed a p53 binding element directly upst
ream of the PTEN gene. Deletion and mutation analyses showed that this elem
ent is necessary for inducible transactivation of PTEN by p53. A p53-indepe
ndent element controlling constitutive expression of PTEN was also identifi
ed. In contrast to p53 mutant cell lines, induction of p53 in primary and t
umor cell lines with wild-type p53 increased PTEN mRNA levels. PTEN was req
uired for p53-mediated apoptosis in immortalized mouse embryonic fibroblast
s. Our results reveal a unique role for p53 in regulation of cellular survi
val and an interesting connection in tumor suppressor signaling.