The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus - Implications for PTEN stability to proteasome-mediated degradation

The tumor suppressor phosphatase PTEN regulates cell migration, growth, and survival by dephosphorylating phosphatidylinositol second messengers and s ignaling phosphoproteins, PTEN possesses a C-terminal noncatalytic regulato ry domain that contains multiple putative phosphorylation sites, which coul d play an important role in the control of its biological activity. The pro tein kinase CK2 phosphorylated, in a constitutive manner, a cluster of Ser/ Thr residues located at the PTEN C terminus, PTEN-phosphorylated defective mutants showed decreased stability in comparison with wild type PTEN and we re more rapidly degraded by the proteasome, Inhibition of PTEN phosphorylat ion by the CK2 inhibitor 5,6-dichloro-1-beta -D-ribofuranosyl-benzimidazole also diminished the PTEN protein content. Our results support the notion t hat proper phosphorylation of PTEN by CK2 is important for PTEN protein sta bility to proteasome-mediated degradation.