0000000001258215
AUTHOR
Rafael Pulido Murillo
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 signaling phosphoproteins. PTEN possesses a C-terminal noncatalytic regulatory domain that contains multiple putative phosphorylation sites, which could play an important role in the control of its biological activity. The protein 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 were more rapidly degraded by the proteasome. Inhibition of PTEN phosphorylation by the CK2 inhibitor…
Phosphorylation-regulated cleavage of the tumor suppressor PTEN by caspase-3: implications for the control of protein stability and PTEN-protein interactions
PTEN phosphatase is one of the most commonly targeted tumor suppressors in human cancers and a key regulator of cell growth and apoptosis. We have found that PTEN is cleaved by caspase-3 at several target sites, located in unstructured regions within the C terminus of the molecule. Cleavage of PTEN was increased upon TNFα-cell treatment and was negatively regulated by phosphorylation of the C-terminal tail of PTEN by the protein kinase CK2. The proteolytic PTEN fragments displayed reduced protein stability, and their capability to interact with the PTEN interacting scaffolding protein S-SCAM/MAGI-2 was lost. Interestingly, S-SCAM/MAGI-2 was also cleaved by caspase-3. Our findings suggest th…