Abstract
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 TNFalpha-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 the existence of a regulatory mechanism of protein stability and PTEN-protein interactions during apoptosis, executed by caspase-3 in a PTEN phosphorylation-regulated manner.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activin Receptors, Type II / metabolism
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Adaptor Proteins, Signal Transducing
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Animals
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Apoptosis / physiology
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COS Cells
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Carrier Proteins / metabolism
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Casein Kinase II
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Caspase 3
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Caspases / metabolism*
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Guanylate Kinases
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Humans
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Kidney / cytology
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Mutagenesis
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PTEN Phosphohydrolase
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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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Protein Serine-Threonine Kinases / metabolism
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Protein Structure, Tertiary
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Proteins*
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Tumor Suppressor Proteins / chemistry
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Magi2 protein, rat
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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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Activin Receptors, Type II
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Guanylate Kinases
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MAGI2 protein, human
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Phosphoric Monoester Hydrolases
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PTEN Phosphohydrolase
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PTEN protein, human
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CASP3 protein, human
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Casp3 protein, rat
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Caspase 3
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Caspases