Abstract
The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual specificity protein phosphatase that dephosphorylates Cdk2 on threonine 160 in a cyclin-dependent manner. To investigate whether mutations of this enzyme occur in hepatocellular carcinoma (HCC), KAP mRNA was analyzed by reverse transcription-PCR (RT-PCR), followed by cloning and sequencing. Eight of 14 biopsy tissues obtained from advanced HCC, 6 of 13 surgically removed HCC tissues, and 2 of the adjacent noncancerous tissues contained aberrant KAP transcripts. Using the yeast two-hybrid system, five of seven representative KAP mutants were shown to be defective in interacting with Cdk2. These data suggest a possible role of KAP mutations in multiple-step hepatocarcinogenesis.
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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CDC2-CDC28 Kinases*
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Carcinoma, Hepatocellular / enzymology*
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Carcinoma, Hepatocellular / genetics
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Cell Cycle Proteins*
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase Inhibitor Proteins
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Cyclin-Dependent Kinases / metabolism
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Dual-Specificity Phosphatases
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Female
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Hepatitis B, Chronic / enzymology
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Hepatitis B, Chronic / genetics
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Hepatitis C, Chronic / enzymology
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Hepatitis C, Chronic / genetics
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Humans
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Liver / enzymology
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Liver / physiology
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Liver Neoplasms / enzymology*
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Liver Neoplasms / genetics
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Male
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Middle Aged
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Molecular Sequence Data
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Mutation
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Protein Serine-Threonine Kinases / metabolism
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Protein Tyrosine Phosphatases / biosynthesis
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Protein Tyrosine Phosphatases / genetics*
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Protein Tyrosine Phosphatases / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
Substances
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor Proteins
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RNA, Messenger
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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CDK2 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases
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CDKN3 protein, human
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Dual-Specificity Phosphatases
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Protein Tyrosine Phosphatases