The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region

摘要: PTEN is a recently identified tumor suppressor inactivated in variety of cancers such as glioblastoma and endometrial prostate carcinoma. It contains an amino-terminal phosphatase domain acts phosphatidylinositol 3,4,5-trisphosphate antagonizing the activity 3-OH kinase. also carboxyl-terminal domain, we addressed role this region that, analogous to target many mutations tumors. Expression mutants PTEN-deficient cells permitted anchorage-independent growth that otherwise was suppressed by wild-type PTEN. The stability these reduced because rapid degradation. Although regulatory PEST sequences PDZ-binding motif, specific elements were dispensable for tumor-suppressor function. study point affecting revealed located strongly predicted β-strands. Surprisingly, affected correlation with degree disruption structural elements. We conclude essential regulating enzymatic are responsible reversion phenotype. propose molecular conformational changes induced constitute mechanism inactivation.