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J. Biol. Chem., Vol. 264, Issue 25, 14762-14768, 09, 1989
SH Huang, JM Tomich, H Wu, A Jong and J Holcenberg
Deoxycytidine kinase (dC kinase) is the rate-limiting enzyme in the
anabolism of important anticancer and retroviral nucleoside derivatives.
Its activity is often decreased in resistance to these drugs. To analyze
the structure, function, and control of this clinically important enzyme we
isolated 15 cDNA clones for human deoxycytidine kinase from lambda gt11
thymus and Molt 4 libraries. Four clones were sequenced. The largest clone
is 2.9 kilobases and codes for a 626-amino acid open reading frame. The DNA
and deduced amino acid sequence of the human dC kinase clones are
homologous with a previously unidentified murine cDNA clone p3.4J
(EMBL:MM34j) reported to be related to granulocyte-macrophage
colony-stimulating factor. Deoxycytidine kinase also has cysteine-rich
regions that are homologous with thioredoxin, the beta subunit of prolyl
4-hydroxylase, phosphoinositide-specific phospholipase C, thyroid
hormone-binding protein, and protein disulfide isomerase. No differences
were seen in the amount and size of deoxycytidine kinase protein and mRNA
between CCRF/CEM and L1210 leukemic cell lines that express and do not
express enzyme activity. Genomic restriction fragments were similar between
the active and inactive CCRF/CEM cell lines. These data suggest that the
cells deficient in dC kinase activity have a small defect in the structural
gene.
Human deoxycytidine kinase. Sequence of cDNA clones and analysis of expression in cell lines with and without enzyme activity
Department of Pediatrics, University of Southern California, Los Angeles 90054-0700.
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