title: Aberrant transcripts of the cyclin-dependent kinase-associated protein phosphatase in hepatocellular carcinoma.
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.
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taipei, Taiwan. catyeh@ms14.hinet.net
authors.forename: C T
authors.initials: CT
authors.lastname: Yeh
authors.forename: S C
authors.initials: SC
authors.lastname: Lu
authors.forename: T C
authors.initials: TC
authors.lastname: Chen
authors.forename: C Y
authors.initials: CY
authors.lastname: Peng
authors.forename: Y F
authors.initials: YF
authors.lastname: Liaw
mesh_terms: D000595:Amino Acid Sequence; D042846:CDC2-CDC28 Kinases; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics; D018797:Cell Cycle Proteins; D051357:Cyclin-Dependent Kinase 2; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D054637:Dual-Specificity Phosphatases; D005260:Female; D019694:Hepatitis B, Chronic / Q000201:enzymology / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000502:physiology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; C084429:CDKN3 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases