Aberrant transcripts of the cyclin-dependent kinase-associated protein phosphatase in hepatocellular carcinoma.
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.
Yeh
C T
CT
Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taipei, Taiwan. catyeh@ms14.hinet.net
Lu
S C
SC
Chen
T C
TC
Peng
C Y
CY
Liaw
Y F
YF
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
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