Disease relevance of UCK1

• The approximately 30-kDa proteins, named UCK1 and UCK2, were expressed in Escherichia coli and shown to catalyze the phosphorylation of Urd and Cyd [1].
• Some properties of uridine-cytidine kinase from a human malignant lymphoma [2].
• The activity of uridine-cytidine kinase (Urd-Cyd kinase). a key enzyme in the salvage of pyrimidine nucleosides, averaged 0.86 +/- 0.16 (S.E.M.) nmole uridine phosphates . min-1 . (mg protein)-1 in fifty-three specimens of human colorectal adenocarcinomas [3].

High impact information on UCK1

• Purification by calcium phosphate gel elution and DEAE chromatography effectively separated this enzyme from cytidine deaminase, which deaminates both CdR and ara-C, and from uridine-cytidine kinase, the enzyme which phosphorylates 5-azacytidine [4].
• No change was observed, however, in the properties of uridine-cytidine kinase, the enzyme responsible for the initial phosphorylation of CPEC; despite this, however, cellular uptake of CPEC was greatly decreased, and phosphorylation of CPEC and its incorporation into RNA were 10-fold less than in the parental cells [5].
• These in vitro studies suggest that 5-azacytidine resistant cells lacking the pyrimidine salvage pathway enzyme uridine-cytidine kinase may be selectively vulnerable to a regimen using pyrimidine antagonists administered in conjunction with the naturally occurring nucleoside uridine [6].
• The genes encoding UCK1 and UCK2 were mapped to chromosome 9q34.2-9q34.3 and 1q22-1q23.2, respectively [1].
• Both ribavirin and viramidine are not phosphorylated by deoxycytidine kinase and uridine-cytidine kinase [7].

Biological context of UCK1

• Upon cytidine binding, a large induced fit was observed at the uridine/cytidine binding site, which endows UCK with a strict specificity for pyrimidine ribonucleosides [8].
• A series of nucleobase-modified analogs of the anticancer compounds 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd) were designed to overcome the strict substrate specificity of the activating uridine-cytidine kinase [9].
• Identification of the former two genes was expected, because the promoter regions of priB and the gene encoding UMP-CMP kinase (uck1) have been shown to contain four or two consensus-like sequences of PRIB binding respectively [10].

Anatomical context of UCK1

• Measurement of UCK activity in these cell lines revealed that it was well correlated with the cells' sensitivity to TAS-106 [11].
• The activity of Urd-Cyd kinase was increased approximately 2.3-fold, and that of OMP decarboxylase by about 91%, while that of FUPRTase was increased by only 27%, as compared to that of normal human colonic mucosa [3].

Associations of UCK1 with chemical compounds

• Uridine-cytidine kinase (UCK), which converts uridine and cytidine to their corresponding monophosphates, is a rate-limiting enzyme involved in the salvage pathway of pyrimidine-nucleotide biosynthesis [12].
• The transport of uridine and 3-deazauridine was compared in two lines of cultured human lymphoblastoid cells that differ in their sensitivity to 3-deazauridine apparently because of reduced uridine-cytidine kinase activity in the resistant line [13].
• In cells pretreated with 3-deazauridine, there was an 80% reduction of intracellular cytidine triphosphate, the natural feedback inhibitor of uridine-cytidine kinase, the rate-limiting enzyme in the phosphorylation of 5-azacytidine [14].
• The phosphorylation of PSI-6130 by recombinant human 2'-deoxycytidine kinase (dCK) and uridine-cytidine kinase 1 (UCK-1) was measured by using a coupled spectrophotometric reaction [15].
• In the case of the uracil enantiomeric pair, this result correlates with an inefficient intracellular monophosphorylation as demonstrated in testing their substrate properties against human uridine-cytidine kinase 1 [16].

Other interactions of UCK1

• It was unclear, however, whether UCK1 or UCK2 is responsible for the phosphorylation of the 3'-ethynyl nucleosides [17].
• In contrast, no mutation in the mRNA or differences in protein expression levels of UCK1 were shown in the EUrd-resistant HT-1080 and NUGC-3 cells [17].
• The roles of uridine-cytidine kinase and CTP synthetase in the synthesis of CTP in malignant human T-lymphocytic cells [18].

Analytical, diagnostic and therapeutic context of UCK1

• Uridine-cytidine kinases (UCK) have important roles for the phosphorylation of nucleoside analogs that are being investigated for possible use in chemotherapy of cancer [1].

References