Author/Authors :
Freeman، نويسنده , , Daniel J. and Li، نويسنده , , Andrew G. and Wei، نويسنده , , Gang and Li، نويسنده , , Heng-Hong and Kertesz، نويسنده , , Nathalie and Lesche، نويسنده , , Ralf and Whale، نويسنده , , Andrew D. and Martinez-Diaz، نويسنده , , Hilda and Rozengurt، نويسنده , , Nora and Cardiff، نويسنده , , Robert D. and Liu، نويسنده , , Xuan and Wu، نويسنده , , Hong، نويسنده ,
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.
