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Vol. 56, Issue 3, 562-569, September 1999
Division of Clinical Virology, Karolinska Institute, Huddinge
University Hospital, Stockholm, Sweden
Phosphorylation of deoxycytidine analogs by cellular enzymes is
a prerequisite for the activity of these compounds. We have investigated the kinetic parameters for the phosphorylation of 1-
-D-arabinofuranosylcytosine (araC) and
2',2'-difluorodeoxycytidine (dFdC) to their diphosphate forms catalyzed
by human UMP-CMP kinase. We cloned the cDNA of this enzyme to enable
characterization of the recombinant protein, determine its expression
in different tissues, and determine the chromosome location of the
gene. We showed that the recombinant UMP-CMP kinase phosphorylated CMP, dCMP, and UMP with highest efficiency and dUMP, AMP, and dAMP with lower efficiency. The monophosphates of araC and dFdC were shown
to be phosphorylated with similar efficiency as dCMP and CMP. We
further showed, in a combined enzymatic assay, that human deoxycytidine
kinase and UMP-CMP kinase together phosphorylated araC, dFdC, and
2',3'-dideoxycytidine to their diphosphate forms. Northern blot
analysis showed that the UMP-CMP kinase mRNA was ubiquitously present
in human tissues as a 3.9-kb transcript with highest levels in
pancreas, skeletal muscle, and liver. The human UMP-CMP kinase gene was
localized to chromosome 1p34.1-1p33 by radiation hybrid analysis. We
further expressed the UMP-CMP kinase as a fusion protein to the green
fluorescent protein in Chinese hamster ovary cells, and showed that the
fusion protein was located in the cytosol and nucleus.
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