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 5,6-dichloro-1-beta-d-ribofuranosyl-benzimidazole also diminished the PTEN protein content. Our results support the notion that proper phosphorylation of PTEN by CK2 is important for PTEN protein stability to proteasome-mediated degradation.
Torres
J
J
Instituto de Investigaciones Citológicas, 46010 Valencia, Spain.
Pulido
R
R
D000595:Amino Acid Sequence; D001943:Breast Neoplasms; D047390:Casein Kinase II; D003001:Cloning, Molecular; D016384:Consensus Sequence; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004795:Enzyme Stability; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007700:Kinetics; D009097:Multienzyme Complexes / Q000378:metabolism*; D016296:Mutagenesis; D051059:PTEN Phosphohydrolase; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D014162:Transfection; D025521:Tumor Suppressor Proteins
D009097:Multienzyme Complexes; D010750:Phosphoproteins; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex