Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Breast Neoplasms
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Casein Kinase II
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Cloning, Molecular
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Consensus Sequence
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Cysteine Endopeptidases / metabolism*
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Enzyme Stability
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Female
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Genes, Tumor Suppressor
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Humans
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Kinetics
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Multienzyme Complexes / metabolism*
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Mutagenesis
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PTEN Phosphohydrolase
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Phosphoproteins / chemistry
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Phosphoproteins / metabolism
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Phosphoric Monoester Hydrolases / chemistry*
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Phosphoric Monoester Hydrolases / genetics
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Phosphoric Monoester Hydrolases / metabolism*
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Phosphorylation
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Proteasome Endopeptidase Complex
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Protein Serine-Threonine Kinases / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Deletion
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Transfection
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Tumor Suppressor Proteins*
Substances
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Multienzyme Complexes
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Phosphoproteins
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Recombinant Proteins
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Tumor Suppressor Proteins
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Casein Kinase II
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Protein Serine-Threonine Kinases
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Phosphoric Monoester Hydrolases
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PTEN Phosphohydrolase
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PTEN protein, human
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex