Enzymatic properties of overexpressed HBV-mevalonate kinase fusion proteins and mevalonate kinase proteins in the human hepatoma cell line PLC/PRF/5.
We have previously reported a case of integration of HBV sequences in the 5'-noncoding region of the gene for mevalonate kinase (Mk) (EC.2.7.1.36) in the human hepatoma cell line PLC/PRF/5, resulting in overexpression of viral-cellular fusion transcripts and enhanced intracellular levels of the enzyme. Here, we present an evaluation of the functionalities of Mk and HBV/Mk fusion proteins derived from viral-cellular fusion- and Mk-transcripts, some of which lack 156 bp in the Mk coding region as a result of a differential splicing process. cDNA clones with a full-length Mk-ORF produce proteins which can metabolize mevalonate to its monophosphorylated form. Our results suggest that the enhanced and inappropriate expression of Mk may lead to increased metabolism of mevalonate and phosphorylation of hitherto unknown cellular proteins. This consequence of HBV-DNA insertion could thus be related to the activation of proteins that may be relevant in oncogenesis.
Graef
E
E
Department of Virus Research, Max-Planck-Institute für Biochemie, Martinsried, Germany.
Caselmann
W H
WH
Hofschneider
P H
PH
Koshy
R
R
D017398:Alternative Splicing; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000821:virology; D002460:Cell Line; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000235:genetics; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000166:cytology; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D014407:Tumor Cells, Cultured
D004279:DNA, Viral; D011506:Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase