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 overexp ression of viral-cellular fusion transcripts and enhanced intracellula r levels of the enzyme. Here, we present an evaluation of the function alities of Mk and HBV/Mk fusion proteins derived from viral-cellular f usion- and Mk-transcripts, some of which lack 156 bp in the Mk coding region as a result of a differential splicing process. cDNA clones wit h a full-length Mk-ORF produce proteins which can metabolize mevalonat e to its monophosphorylated form. Our results suggest that the enhance d and inappropriate expression of Mk may lead to increased metabolism of mevalonate and phosphorylation of hitherto unknown cellular protein s. This consequence of HBV-DNA insertion could thus be related to the activation of proteins that may be relevant in oncogenesis. (C) 1995 A cademic Press, Inc.