The most recent information on DCK is here. Click here for the function of DCK. Edit this page in Wiki Genes - DCK or see Wiki Gene. The brain tumor samples expressed low levels of dCK. Paper-10615272. Human deoxycytidine kinase is located in the cell nucleus. Paper-1225643. The degree of dCK gene expression varied over a 50-fold range. Paper-1738979. Human deoxycytidine kinase as a conditional mutator in Escherichia coli. Paper-1129193. Human deoxycytidine kinase as a conditional mutator in Escherichia coli. Paper-1043706. No other tested L-adenosine or L-guanosine analog was a substrate of dCK. Paper-2081613. Deoxycytidine kinase activity is abundant in human T and B lymphocytes. Paper-5174143. Sequencing of the dCK coding region showed point mutations in seven patients. Paper-8226541. Biological activity of 1-deazapurine nucleosides: role of deoxycytidine kinase? Paper-1945828. The KB-Gem clone's DCK enzyme activity was 56% of that of the parental cell line. Paper-1992285. Deoxycytidine Kinase is Reversibly Phosphorylated in Normal Human Lymphocytes. Paper-12290088. The amino acid sequence of the DCK protein and mRNA expression remained unchanged. Paper-1992285. Because of these complex results, dCK kinetics were studied in greater detail. Paper-567005. No inhibition of dCK-mediated dCyd phosphorylation was found by either araG or dFdG. Paper-1588939. Deoxyguanosine phosphorylation is associated with deoxycytidine kinase. Paper-5050566. Deoxycytidine kinase: properties of the enzyme from human leukemic granulocytes. Paper-2381542. In contrast, deoxycytidine was found to prevent stimulation of dCK by various drugs. Paper-11286292. Characterization of the deoxycytidine kinase promoter in human lymphoblast cell lines. Paper-194009. The expression of dCK has been postulated to be correlative of gemcitabine resistance. Paper-11824039. Dexamethasone with verapamil decreased deoxycytidine kinase activity in 2R160. Paper-8944218. Fluorescence studies of substrate binding to human recombinant deoxycytidine kinase. Paper-10871441. Additionally, the expression of dCK was estimated, in medullary thyroid carcinoma (MTC). Paper-11037631. Kinetics of phosphorylation of 5-aza-2'-deoxyycytidine by deoxycytidine kinase. Paper-3324737. Derivatives of L-adenosine and L-guanosine as substrates for human deoxycytidine kinase. Paper-1945816. The mitochondrial deoxycytidine kinase was localized to the outer mitochondrial membrane. Paper-7896350. These structures illuminate the phosphoryl donor binding and preference mechanisms of dCK. Paper-10830659. Sequencing of dCK mRNA did not reveal alternate splicing or mutations in the coding region. Paper-10847043. Elucidation of different binding modes of purine nucleosides to human deoxycytidine kinase. Paper-12933481. G-phase lymphocytes showed a higher sensitivity for dCK stimulation than S-phase cells. Paper-2112488. This is in line with substrate specificity tests, which revealed a very low affinity of dCK. Paper-1945828. Unexpectedly, alpha-dideoxycytidine ( ddC) was a 3-fold better substrate for dCK than beta-ddC. Paper-2062256. HepG2 hepatocellular carcinoma cells were used to study the transcriptional regulation of dCK. Paper-10053052. This study found novel DCK polymorphisms, including nonsynonymous SNPs, in exons 3 and 6. Paper-12154100. The prodrug was active in cell growth inhibition regardless of the deoxycytidine kinase level. Paper-1110641. The enzyme activity in liver metastases was correlated to dCK mRNA expression (r=0.497, P=0.05). Paper-9668165. The Km and Vmax of dCyd for HL-60 dCK were similar to those for 5-Aza-C-induced HL-60/ Ara-C dCK. Paper-6903283. The decreased expression of dCK also resulted in lower activity in both Ara-C resistant variants. Paper-13665035. It is formed intra-cellularly via the phosphorylation of gemcitabine by deoxycytidine kinase. Paper-12345706. These data suggest a critical role for cytoplasmic dCyd kinase in the mitochondrial toxicity of ddC. Paper-52401. Retroviral transfer of deoxycytidine kinase into tumor cell lines enhances nucleoside toxicity. Paper-543145. The phosphorylation of CdA in crude extracts showed a close correlation to the dCK polypeptide level. Paper-208674. As a purine-nucleoside analog, clofarabine is a better substrate of dCK than deoxycytidine. Paper-10824771. The longest open reading frame encoded a protein that was 48% identical to dCK at the amino acid level. Paper-602918. Defective expression of deoxycytidine kinase in cytarabine-resistant acute myeloid leukemia cells. Paper-13665035. New targets for pyrimidine antimetabolites for the treatment of solid tumours. 2: Deoxycytidine kinase. Paper-8130340. The normal dCK activities with deoxycytidine as substrate varied between 0.8 and 13 nmol/hr/10(6) cells. Paper-567005. The increase in araG phosphorylation was shown to be due to increased expression of deoxycytidine kinase. Paper-13321551. Deletion mutants of human deoxycytidine kinase mRNA in cells resistant to antitumor cytosine nucleosides. Paper-9032875. Substrate specificity of human deoxycytidine kinase toward antiviral 2',3'-dideoxynucleoside analogs. Paper-7243314. Gemcitabine's mechanism of action is activated by deoxycytidine kinase to dFdCMP, dFdCDP and dFdCTP. Paper-1937594. The capacity of T cells (CCRF-CEM) to accumulate ara-GTP was dependent primarily on deoxycytidine kinase. Paper-4967089. Kinetic analysis of human deoxycytidine kinase with the true phosphate donor uridine triphosphate. Paper-1054040. CONCLUSION: dCK mRNA expression is a candidate indicator for GEM efficacy in unresectable pancreatic cancer. Paper-13870537. Of the purine analogs tested as substrates for dCK, only CdA could compete with 2'-deoxycytidine (dCyd). Paper-1588939. Deoxyguanosine-phosphorylating activity eluted as a single peak in association with deoxycytidine kinase. Paper-4505526. Purification and characterization of deoxycytidine kinase from acute myeloid leukemia cell mitochondria. Paper-7896350. Activation of deoxycytidine kinase by UV-C-irradiation in chronic lymphocytic leukemia B-lymphocytes. Paper-9743106. Thus, further modification at the 3-position of the coumarin ring can improve the potency of new DCK analogues. Paper-10361357. DCK expression in cultured lymphoblast cell lines is not solely a function of the T or B lineage derivation. Paper-194009. Recently, crystal structures of dCK (dCKc) with various pyrimidine nucleosides as substrates have been reported. Paper-11298743. In addition, dCK activity and mean mRNA levels were 2.5-fold higher in the metastases than in the liver samples. Paper-9668165. Resistance to 1,25-dihydroxyvitamin D3 of a deoxycytidine kinase-deficient variant of human leukemia HL60 cells. Paper-74191. These results indicate that the gemcitabine resistance phenotype is stable and mainly due to dCK deficiency. Paper-386069. Deoxycytidine kinase from a variety of animal tissues binds to Cibacron Blue 3G-A coupled to Sepharose CL-6B. Paper-3036408. The reaction depended on inorganic phosphate, and dCK showed maximum cleavage activity between pH 7 and pH 8. Paper-10563676. Regulation of purine deoxynucleoside phosphorylation by deoxycytidine kinase from human leukemic blast cells. Paper-6143338. However, we have discovered that human recombinant 2'-deoxycytidine kinase ( dCK) phosphorylates ( S,S)-isoddA. Paper-8624030. When cells were gamma-irradiated in the presence of calyculin A, a more pronounced activation of dCK was observed. Paper-9740656. Current assays to measure DCK expression and activity require biopsy samples and are prone to sampling errors. Paper-13631913. Induction of deoxycytidine kinase by 5-azacytidine in an HL-60 cell line resistant to arabinosylcytosine. Paper-6903283. Deoxycytidine kinase expression and activity in patients with resistant versus sensitive acute myeloid leukemia. Paper-9571294. Elevated ratio between deoxycytidine kinase and thymidine kinase 2 in CLL lymphocytes compared to control cells. Paper-8242526. Ara-C is phosphorylated by deoxycytidine kinase, which is subject to negative allosteric regulation by dCTP. Paper-9523658. Two-hour exposure of human tonsillar lymphocytes to 2-chloro-deoxyadenosine (CdA) led to a two-fold activation of dCK. Paper-10615271. Four isomeric methyl substituted DCK analogues (2-5) were asymmetrically synthesized from different starting materials. Paper-1697375. Extending thymidine kinase activity to the catalytic repertoire of human deoxycytidine kinase. Paper-13853077. Selective increase of dATP pools upon activation of deoxycytidine kinase in lymphocytes: implications in apoptosis. Paper-10615271. Here we showed that dCK overexpressed in HEK 293T cells was labeled after incubating the cells with [ 32P]orthophosphate. Paper-11317053. In addition a deletion in one of the alleles of the deoxycytidine kinase was detected in the fludarabine-resistant line. Paper-1956175. In CEM/ dCk- cells DNA hypomethylation between 50 and 25% of control was seen only after treatment with DHAC and 5-aza-C. Paper-5621301. The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation. Paper-10824771. At 1 and 10 muM of deoxycytidine the effects of CTP on dCK activity in A2780, C26-10 and WiDr cells were less pronounced. Paper-567005. Pyrimidine salvage enzymes in human tonsil lymphocytes: II. Purification and properties of deoxycytidine kinase. Paper-5105336. Expression and substrate specificities of human thymidine kinase 1, thymidine kinase 2 and deoxycytidine kinase. Paper-7083292. The dCk activity was increased after treatment with the 5-aza-C nucleosides approximately 10% compared to untreated cells. Paper-5621301. Functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells. Paper-9370376. Taken together, these findings demonstrate that dCK can regulate the in vitro cellular response to Ara-C in AML cells. Paper-13665035. Accordingly, HuR overexpression elevates, whereas HuR silencing reduces, dCK protein expression in pancreatic cancer cells. Paper-13814176. Dideoxycytidine metabolism in wild type and mutant CEM cells deficient in nucleoside transport or deoxycytidine kinase. Paper-6251660. No correlations were found between TK or dCK activities and plasma viral load, CD4 cell count, sex or age of patients. Paper-11003703. We show that several hydrophobic residues at position 104 endow dCK with thymidine kinase activity. Paper-13853077. Ion-exchange chromatography showed the same profile of deoxycytidine kinase activity in resting and proliferating cells. Paper-5953872. 3'-Azido-2',3'-dideoxythymidine induced deficiency of thymidine kinases 1, 2 and deoxycytidine kinase in H9 T-lymphoid cells. Paper-9513359. Thymidine is phosphorylated by both thymidine kinases, and deoxycytidine is phosphorylated by both dCK and TK2. Paper-7217313. Binding of substrates to human deoxycytidine kinase studied with ligand-dependent quenching of enzyme intrinsic fluorescence. Paper-7567344. Furthermore, homology of the peptide sequences od dCK to parts of thymidine kinases and protein-tyrosine kinases are detected. Paper-6966857. This may be due in part to a difference in the behavior of L(-)Fd4C and L(-)SddC ( 3TC) towards cytosolic deoxycytidine kinase. Paper-1569979. Enhancement of cytarabine sensitivity in squamous cell carcinoma cell line transfected with deoxycytidine kinase. Paper-9479510. Identification of in vivo phosphorylation sites on human deoxycytidine kinase. Role of Ser-74 in the control of enzyme activity. Paper-11317053. Increased ratio between deoxycytidine kinase and thymidine kinase 2 in CLL lymphocytes compared to normal lymphocytes. Paper-312363. Relationship of deoxycytidine kinase and cytoplasmic 5'-nucleotidase to the chemotherapeutic efficacy of 2-chlorodeoxyadenosine. Paper-7582998. METHODS: Cell growth of CHO and 3T6 cells of known deoxycytidine kinase level was determined in the presence of N3Urd and N3Cyd. Paper-1110641. The enhancement of dCK activity by dThd-5'-TS can be reversed by dCyd, but dThd had no effect on the enzyme activation in cells. Paper-9743105. Selective activation of deoxycytidine kinase by thymidine-5'-thiosulphate and release by deoxycytidine in human lymphocytes. Paper-9743105. The effects of high salt concentrations on the regulation of the substrate specificity of human recombinant deoxycytidine kinase. Paper-1215436. Cell survival, inhibition of DNA synthetic capacity (DSC), ara-CTP anabolism, and dCk enzymatic characteristics were studied. Paper-147555. According to this model, extracellular deoxycytidine at micromolar concentrations is efficiently salvaged by deoxycytidine kinase. Paper-4422037. Regulation of deoxycytidine kinase by deoxycytidine and deoxycytidine 5' triphosphate in whole leukemia and tumor cells. Paper-1483901. CONCLUSIONS: In the dFdC-resistant lung tumor cell line SWg, the deficiency in dCK is related to the resistance to dFdC and ara-C. Paper-9535283. The possibility of interference of nucleoside analogues with the mechanisms of posttranslational modification of dCK was proposed. Paper-1483976. Expression of deoxycytidine kinase and phosphorylation of 2-chlorodeoxyadenosine in human normal and tumour cells and tissues. Paper-208674. Resistance to 1-beta-D-arabinofuranosylcytosine in human T-lymphoblasts mediated by mutations within the deoxycytidine kinase gene. Paper-7342754. The purification of deoxycytidine kinase from human leucemic spleen reported here result in a pure protein of molecular weight 28K. Paper-5189886. Expression of deoxycytidine kinase in leukaemic cells compared with solid tumour cell lines, liver metastases and normal liver. Paper-9668165. In this study, we show that dCK overexpressed in HEK-293T cells was labelled after incubation of the cells with [ 32P]orthophosphate. Paper-12290087. DCK lactam analogues were synthesized and evaluated for anti-HIV activity against HIV-1 replication in H9 lymphocyte cells. Paper-8483871. Gemcitabine is phosphorylated by deoxycytidine kinase and thymidine kinase 2 and during S-phase incorporated into DNA. Paper-8944218. In the current study, the crystal structure of clofarabine- and ADP-bound dCK was solved to 2.55 angstroms by molecular replacement. Paper-10824771. Cortisol decreased deoxycytidine kinase activity in SW1573 cells and cortisol with verapamil in 2R120 and 2R160 cells. Paper-8944218. Here, the functional involvement of dCK in gemcitabine-resistance of pancreatic cancer was investigated. Paper-12920813. Paclitaxel did not affect deoxycytidine kinase levels, but ribonucleotide levels increased possibly explaining the increase in dFdCTP. Paper-8533261. We also established an in vitro model of Ara-C resistance using phosphorothioate antisense oligonucleotides to dCK (dCK-AS). Paper-8388377. Here, the structures of dCK complexes with the products dCMP, UDP and Mg(2+) ion, and with dAMP, UDP and Mg(2+) ion are reported. Paper-12644112. Immunocytochemical detection of deoxycytidine kinase in pediatric malignancies in relation to in vitro cytarabine sensitivity. Paper-10615272. Compared to most other cell types, monocytes and macrophages have very low dCTP pools, but abundant deoxycytidine kinase activity. Paper-48083. Structural analysis of the deoxycytidine kinase gene in patients with acute myeloid leukemia and resistance to cytosine arabinoside. Paper-8226541. KY-Ra showed the same restriction pattern of genomic DNA and the same nucleotide sequences of the dCK gene as the parental cell line. Paper-8109974. Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients. Paper-10849808. The interactions between 2-Cl and its surrounding hydrophobic residues contribute to the high catalytic efficiency of dCK for clofarabine. Paper-10824771. The results indicate that ddAdo may be phosphorylated in T cells by several different enzymes, although deoxycytidine kinase predominates. Paper-6005712. G-phase enriched tonsilar lymphocyte subpopulation treated by CdA showed more profound stimulation of dCK activity than S-phase cells. Paper-1483976. However, the moderately 3TC-resistant phenotype of CEM(ZLA) cannot be ascribed to a similar reduction in deoxycytidine kinase activity. Paper-12290937. This catalytic activity is important for the design of in vitro experiments with dCK, such as crystallization and NMR spectroscopy. Paper-10563676. A deoxycytidine kinase-deficient mutant neither accumulated dFdCTP nor showed any cytotoxic response up to drug concentrations of 100 microM. Paper-6076576. These results indicated that dCK may exist as a phosphoprotein in vivo and that its activity can be correlated with its phosphorylation level. Paper-11317053. We show that, remarkably, MTX enhances incorporation and cytotoxicity of ara-C through regulation of dCK activity in Burkitt's lymphoma cells. Paper-12283944. Therefore, it is highly unlikely that DNA methylation plays a role in the suppression of dCK gene expression in these cell lines. Paper-1564038. Furthermore, the cytoplasmic deoxycytidine kinase (dCyd kinase)-deficient CEM cells were highly resistant to the mitochondrial toxicity of ddC. Paper-52401. PCR analysis showed that ZD6474 increased the ratio between gene expression of deoxycytidine kinase and ribonucleotide reductase. Paper-12344999. Positive regulation of deoxycytidine kinase activity by phosphorylation of Ser-74 in B-cell chronic lymphocytic leukaemia lymphocytes. Paper-13283212. Activation of deoxycytidine kinase during inhibition of DNA synthesis by 2-chloro-2'-deoxyadenosine ( Cladribine) in human lymphocytes. Paper-1616837. Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer. Paper-12920813. This study investigated the regulation of dCK activity in response to UV-C light, a condition which causes DNA lesions and DNA repair synthesis. Paper-9743106. METHODS AND MATERIALS: All seven DCK exons and the promoter region were sequenced from 100 healthy volunteers (79 females and 21 males). Paper-12154100. This is the first report showing that the down regulation of dCK gene expression may be affected by a different mechanism than mutation. Paper-8109974. Docking simulation with a purine nucleoside specific homology model of deoxycytidine kinase, a target enzyme for anticancer and antiviral therapy. Paper-11298743. The relation between deoxycytidine kinase activity and the radiosensitising effect of gemcitabine in eight different human tumour cell lines. Paper-12069381. The phosphorylation of gemcitabine into the active gemcitabine triphosphate ( dFdCTP) is catalyzed by deoxycytidine kinase. Paper-8278215. The phosphorylation of gemcitabine into the active gemcitabine triphosphate ( dFdCTP) is catalyzed by deoxycytidine kinase. Paper-8282928. The rate-limiting step in the formation of triphosphate is conversion of F-ara-A to its monophosphate, which is catalyzed by deoxycytidine kinase. Paper-9399604. The substrate specificity of Cys-185-Ala dCK was altered in that dAdo and UTP were better substrates for the mutant than for the wild-type enzyme. Paper-11802683. The human deoxycytidine kinase gene is a single copy gene and is comprised of seven exons that are spread over more than 34 kb of the genome. Paper-7654257. Although compelling evidence indicated that dCK activity might be regulated by phosphorylation/dephosphorylation, direct demonstration was lacking. Paper-11317053. Lymphoblast cell lines from subjects heterozygous for the coding changes had significantly lower DCK activity compared with homozygous WT subjects. Paper-12544285. In addition, these cell lines were also resistant to azidothymidine and had reduced deoxycytidine kinase and thymidine kinase activities. Paper-2000133. The role of cytoplasmic deoxycytidine kinase in the mitochondrial effects of the anti-human immunodeficiency virus compound, 2',3'-dideoxycytidine. Paper-52401. Thymocytes also formed a small amount of deoxyguanosine triphosphate (dGTP), presumably through direct phosphorylation by deoxycytidine kinase. Paper-6535898. The dCK-targeting siRNA significantly reduced gemcitabine sensitivity (p < 0.01) without affecting cell proliferation. Paper-12920813. We report a procedure for the purification of a novel deoxycytidine kinase (52 kDa) from isolated human peripheral blood leukemia cell mitochondria. Paper-7896350. The kinetics and regulation of nucleoside phosphorylation by highly purified human deoxycytidine kinase from leukemic lymphoblasts were studied. Paper-6143338. Additionally, in vitro assays using BM cells from AML patients revealed that the expression of dCK and the sensitivity to Ara-C were correlated. Paper-13665035. Interaction between fludarabine or cladribine with deoxycytidine kinase results in a significant enhancement of the activity of cytarabine. Paper-8549634. Thymidine kinase and deoxycytidine kinase activity in mononuclear cells from antiretroviral-naive HIV-infected patients. Paper-11003703. A dose-dependent inhibition of dCK was observed, highlighting this kinase as a possible additional secondary molecular target for imatinib. Paper-11093813. Nanomolar concentrations of CdA blocked the proliferation of lymphoblastoid cell lines with a high ratio of deoxycytidine kinase to deoxynucleotidase. Paper-4437070. 2',3'-Dideoxynucleoside phosphorylation by deoxycytidine kinase from normal human thymus extracts: activation of potential drugs for AIDS therapy. Paper-5619137. Purine deoxyribonucleosides were also efficiently phosphorylated by dCK but in this case sugar modifications led to drastically decreased activity. Paper-6976012. Phytohemaglutinine stimulation of normal lymphocytes did not lead to any substantial increase in either dCK activity or expression (less than 2.5-fold). Paper-7988697. It is concluded that an increased expression of mRNA, specific for TK1, dCK and dThdPase, may be involved in carcinogenic processes in the human thyroid. Paper-11037631. The dCk activity was increased up to 37% after treatment with DHAC or 5-aza-C but no increase was observed after treatment with 5-aza-Cdr or ara-AC. Paper-5621301. The sequence variation analysis using bisbenzimide/ polyethylene glycol electrophoresis demonstrated no sequence alteration of dCK cDNA in all cases. Paper-1738979. A study was performed to investigate if there was a correlation between the dCK levels and the response to CdA treatment.(ABSTRACT TRUNCATED AT 400 WORDS) Paper-7988697. In contrast, 2',3'-dideoxyadenosine was phosphorylated by the deoxycytidine kinase-deficient mutant and retained anti-HIV activity in this cell line. Paper-6006419. Structural basis for activation of the therapeutic L-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase. Paper-12424560. 2,5-Difluoro-4-[1-(2-deoxy-beta-L-ribofuranosyl)]-aniline (JW5), a L-nucleoside mimic, was phosphorylated up to 15% as efficiently as deoxycytidine by dCK. Paper-10892002. Extracts from CdA-treated cells were much better recognized by the antibody raised against the C-terminal peptide of dCK than the BAPTA-AM-treated samples. Paper-10406182. Steady-state intrinsic fluorescence measurements were used to study interaction of dCK with substrates in the absence and presence of phosphate donors. Paper-10871441. In vitro apricitabine competes with other deoxycytidine analogues for intracellular phosphorylation mediated by deoxycytidine kinase. Paper-13348236. Comparison of the substrate specificities of human thymidine kinase 1 and 2 and deoxycytidine kinase toward antiviral and cytostatic nucleoside analogs. Paper-6976012. Cell survival was determined 7, 8, or 9 days after RT by the sulforhodamine B test. dCK activity of the cells was determined by an enzyme activity assay. Paper-12069381. We propose, therefore, that the TKs of herpesviruses of higher and lower vertebrates have evolved, either independently or successively, from a cellular dCK. Paper-6982414. 3-Hydroxymethyl DCK (6) exhibited potent anti-HIV activity in H9 lymphocytes with EC(50) and TI values of 1.87 x 10(-4) microM and 1.89 x 10(5), respectively. Paper-9108760. These data will be used to assess the effect of DCK candidate SNPs (promoter, exons 3 and 6) in patients receiving gemcitabine anticancer treatment. Paper-12154100. After pulsed low dose rate irradiation the activities of deoxycytidine kinase and thymidine kinase 1 and 2 were increased 1.5-2-fold 6 h after treatment. Paper-9346173. We conclude that down-regulation of dCK in cells resistant to CdA and CAFdA and increased activity of RR in cells resistant to Fara-A contribute to resistance. Paper-9775126. The crystal structure of dCK has been solved previously in complex with pyrimidine nucleosides and ADP [Sabini et al. (2003), Nature Struct. Biol. 10, 513-519]. Paper-10824771. Forty-three pyrimidine derivatives, mainly containing the 4-aminopyrimidine system, have been prepared and evaluated as inhibitors of deoxycytidine kinase. Paper-2790239. Phytohaemagglutinin stimulation of normal lymphocytes did not lead to any substantial increase in either dCK activity or protein expression (less than 2.5-fold). Paper-208674. In colon adenocarcinomas, the dCK content was significantly higher (20 +/- 9 ng/mg, n = 20) than in normal colon mucosa (8 +/- 3.5 ng/mg, n = 19, P < 0.05). Paper-208674. A similar pattern of dCK expression was found in gastric adenocarcinomas (21 +/- 13 ng/mg, n = 5) and normal stomach mucosa (6 +/- 5 ng/mg, n = 5, P < 0.15). Paper-208674. In conclusion, the efficiency of dCK (Vmax/Km ratio) seems to correlate with accumulation of dFdCTP, the active metabolite of dFdC, and with cellular sensitivity. Paper-567005. Activation of deoxycytidine kinase by deoxyadenosine: implications in deoxyadenosine-mediated cytotoxicity. Paper-11286292. The enzyme activity and protein expression levels of dCK in the cell lines were closely related to the mRNA expression levels (r=0.75, P=0.026 and r=0.86, P=0.007). Paper-9668165. Several series of mono- and di-substituted DCK derivatives (DCKs) have previously been synthesized, and their structure-activity relationships are well established. Paper-11535336. Cyclopentenyl cytosine-induced activation of deoxycytidine kinase increases gemcitabine anabolism and cytotoxicity in neuroblastoma. Paper-10564553. In colon adenocarcinomas, the dCK content was significantly higher (21 +/- 9.3 ng/mg, n = 20) than in normal colon mucosa (8.2 +/- 3.7 ng/mg, n = 19, p < 0.05). Paper-7988697. The formation of free nucleobases occurred only with reduced dCK, because the reaction was highly dependent on the presence of reducing agents such as dithiotreitol. Paper-10563676. These results suggest that the phosphorylation of pharmacologically active purine nucleosides by deoxycytidine kinase is regulated by cellular nucleotide pools. Paper-6143338. The cells described here may contribute to the study of a novel mechanism associated with Ara-C resistance, in which reduced dCK activity may play an important role. Paper-8388377. In the liver samples, these were not correlated. dCK mRNA expression showed only a 36-fold range in liver while a 150-fold range was observed in the liver metastases. Paper-9668165. Isolation and characterization of a deoxycytidine kinase-deficient human promyelocytic leukemic cell line highly resistant to 1-beta-D- arabinofuranosylcytosine. Paper-4532172. Taken together, these results indicate that deoxycytidine kinase and the es nucleoside transporter are targets for manipulation of the metabolism and activity of 3TC. Paper-1104851. Deoxycytidine kinase is a key anabolic enzyme for the activation of ara-C and other antitumor drugs, as well as normal purine and pyrimidine deoxynucleotides. Paper-7896350. Thus, dCK is expressed constitutively and predominantly in lymphoid cells, but it is also found in solid non-lymphoid tissues, with increased levels in malignant cells. Paper-208674. In vitro, accumulation of [(18)F]FAC in murine and human leukemia cell lines is critically dependent on DCK activity and correlates with dFdC sensitivity. Paper-13631913. However, the only strong correlations with gemcitabine sensitivity are dCK activity and dFdCTP pools, with a potential important role for ribonucleotide reductase. Paper-9185908. Thus resistance to ddC toxicity may be due to cells' decreased ability to accumulate intracellular ddC anabolites, which may depend on cytoplasmic deoxycytidine kinase. Paper-420892. Effect of 5-azacytidine and congeners on DNA methylation and expression of deoxycytidine kinase in the human lymphoid cell lines CCRF/CEM/0 and CCRF/CEM/dCk-1. Paper-5621301. Gemcitabine exposure to pancreatic cancer cells enriches the association between HuR and dCK mRNA and increases cytoplasmic HuR levels. Paper-13814176. A prodrug of 5'-monophosphate of N3Urd was prepared and its biological activity was evaluated with CHO cells as well as with cells transfected with deoxycytidine kinase. Paper-1110641. A similar pattern of dCK expression was found in gastric adenocarcinomas (21 +/- 13 ng/mg, n = 5) and normal ventricular mucosa (6.2 +/- 5.4 ng/mg, n = 5, p < 0.15). Paper-7988697. Deoxycytidine kinase, which phosphorylates deoxycytidine (CdR) and its analog, cytosine arabinoside (ara-C), has been purified 71-fold from human leukemic cells. Paper-2381542. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival. Paper-11824039. Fluorescence energy transfer studies of human deoxycytidine kinase: role of cysteine 185 in the conformational changes that occur upon substrate binding. Paper-11802683. Whereas TK1 is only responsible for thymidine phosphorylation, dCK is capable of converting dC, dA, and dG into their monophosphate forms. Paper-13853077. AG6000 is cross-resistant to other drugs that require activation by dCK, such as I-beta-D-arabinofuranosylcytosine, 5-aza-2'-deoxycytidine, and 2-chlorodeoxyadenosine. Paper-386069. Time course of enhanced activity of deoxycytidine kinase and thymidine kinase 1 and 2 in cultured human squamous lung carcinoma cells, SW-1573, induced by gamma-irradiation. Paper-12223379. New phenolic and aza 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone ( DCK) analogs were synthesized and assayed for inhibition of HIV-1 IIIB replication in H9 lymphocytes. Paper-12556750. With activity against resting and dividing cells that express high deoxycytidine kinase activity, cladribine causes prolonged, profound suppression of lymphocyte counts. Paper-12551572. Modulation of deoxycytidine kinase activity has already been shown to be an effective way to improve the effect of cytarabine and will probably be a target for new therapies. Paper-8130340. Despite similar deoxycytidine kinase activity and unchanged uptake of nucleosides such as AZT and 2'-deoxycytidine, CEM 3TC had profoundly impaired 3TC accumulation. Paper-9240084. Complete repair of gamma-irradiated DNA was detected within 1 hr following the irradiation along with dCK activation, but the rate of repair was not accelerated by calyculin A. Paper-9740656. The mechanism for the effects of 0.4 M NaCl on dCK kinetic behaviour is not known but it is most likely due to alterations in the conformation of the active site of the enzyme. Paper-1215436. Thus, HSV-TKIGCV demonstrated the widest therapeutic index, while CD/5FC and NTR/ CB1954 showed the stronger bystander effect than HSV-TK/GCV. dCK/AraC had little efficacy. Paper-1504225. 3-DU is an interesting agent to use in combination with ARA-C, since drug-resistant cells that are deficient in deoxycytidine kinase are very sensitive to this uridine analogue. Paper-6978692. Deoxycytidine kinase is an enzyme required for the activation of, for example, cytarabine, the most widely used agent for the chemotherapy of haematological malignancies. Paper-8130340. Phase II trial of 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate in non-Hodgkin's lymphoma: prospective comparison of response with deoxycytidine kinase activity. Paper-5751017. Although UTP is the preferred phosphoryl donor for this reaction, our previous studies reported dCK structures solely containing ADP in the phosphoryl donor binding site. Paper-10830659. Our results are in agreement with earlier studies with partially purified calf thymus deoxycytidine, but clearly different from some studies on human deoxycytidine kinase. Paper-5189886. Here we present kinetic data on several dCK variants where Arg104 has been replaced by select residues, all performed in combination with the mutation of Asp133 to an alanine. Paper-13853077. In both CEPH and YRI subjects, the C allele of a 3'-untranslated region single-nucleotide polymorphism (SNP) (35708 C>T) was significantly associated with lower DCK mRNA expression. Paper-12544285. Deoxycytidine kinase was shown to be activated during 2-chlorodeoxyadenosine (CdA) treatment of human lymphocytes, under the conditions when the DNA synthesis is inhibited. Paper-1483953. 2-Chlorodeoxyadenosine ( cladribine, CdA) and 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine (CAFdA) are purine nucleoside analogues which are also phosphorylated by dCK. Paper-1564038. Inhibition by deoxycytidine of the 5'-phosphorylation of 3TC in duck hepatocytes confirmed that, as in mammalian cells, deoxycytidine kinase catalyzed 3TC activation. Paper-1104851. DCK and HENT1 expression levels were significantly lower in children with MLL gene-rearranged ALL compared to children with MLL germ line ALL (P = 0.0003 and 0.03, respectively). Paper-12344634. Reconstitution of a deoxycytidine kinase-deficient cell line with the wild-type nuclear or the mutant cytosolic enzymes both restored sensitivity toward anticancer nucleoside analogs. Paper-1225643. Unlike 1-beta-D-arabinofuranosylcytosine which is activated by deoxycytidine kinase, the enzyme responsible for the phosphorylation of CPE-C is uridine/ cytidine kinase. Paper-7399176. Steady-state and time-resolved fluorescence of human deoxycytidine kinase was used to study its interaction with the substrates dCyd, dAdo, dUrd, dTTP, and the feedback inhibitor dCTP. Paper-7567344. Intracellular cytarabine triphosphate production correlates to deoxycytidine kinase/cytosolic 5'-nucleotidase II expression ratio in primary acute myeloid leukemia cells. Paper-13762780. Activation of dCK by a number of genotoxic agents including 2-chlorodeoxyadenosine, a deamination-resistant deoxyadenosine analogue, was found previously. Paper-11286292. These results clearly demonstrate that a major mechanism of ara-C resistance of these human KB cells was a decrease in the activity of the ara-C activating enzyme deoxycytidine kinase. Paper-4654374. A series of disubstituted 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone ( DCK) analogues (1-10) were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. Paper-8717559. In light of this, the potential contribution of dCK activation to apoptosis induction--presumably by supplying dATP or its analogues for the apoptosome formation--deserves consideration. Paper-10615271. Site-directed mutagenesis of a putative nuclear targeting signal, identified in the primary structure of deoxycytidine kinase, completely abolished nuclear import of the protein. Paper-1225643. As a result of dCK expression, MCF-7 cells demonstrated a 2.5-fold increase in drug sensitivity to 1-beta-D-arabinofuranosylcytosine ( AraC) and 2-chloro-2'-deoxyadenosine (CdA). Paper-543145. These data indicate that the intracellular metabolism of 2',3'-dideoxycytidine in CEM cells is initiated by the nucleoside transport system and the cellular deoxycytidine kinase activity. Paper-5954968. However, the binding of dCyd to dCK in the presence of ATP or UTP was accompanied by a 1.5- or 3-fold higher quenching amplitude as compared with dCyd alone or in the presence of AMP-PNP. Paper-1909332. Fowlpox virus encodes a protein related to human deoxycytidine kinase: further evidence for independent acquisition of genes for enzymes of nucleotide metabolism by different viruses. Paper-108687. Furthermore, pretreatment with pemetrexed resulted in an increased deoxycytidine kinase expression concomitant with the alteration of the resistance to gemcitabine in H23/GEM-R cells. Paper-12165139. The amount of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate formed in tissues has been shown to be influenced by the relative levels of deoxycytidine kinase and cytosine deaminase. Paper-3038939. Energy transfer studies of transfer between Trp residues of dCK and the fluorescent probe N-(1-pyrene)maleimide (PM), which specifically labels Cys residues in proteins, were performed. Paper-11802683. Metabolism of deoxycytidine to dCTP inhibits phosphorylation of cytosine arabinoside (araC), fludarabine (FaraA) and 2-chlorodeoxyadenosine (CdA) by deoxycytidine kinase. Paper-1076582. BAPTA-AM, a cell-permeable calcium chelator selectively inhibited the activation of dCK in a time- and concentration-dependent manner while extracellular calcium depletion had no effect. Paper-10406182. Expression of dCK was slightly increased in cells resistant to lower concentrations of gemcitabine, but was decreased below the undetectable level in higher concentration-resistant subclones. Paper-13101080. Thymidine and fludarabine, which are agents that enhance the activity of deoxycytidine kinase, were tested in strategies for increasing the cellular content of 3TC 5'-phosphates. Paper-1104851. CONCLUSION: Down-regulation of dCK specifically enhanced acquired resistance to gemcitabine in pancreatic cancer cells without affecting their proliferation. Paper-12920813. Also, no major differences in wt dCK expression and activity were observed between samples obtained from patients with AML and bone marrow or peripheral blood samples from healthy donors. Paper-9571294. Selective inactivation of the deoxyadenosine phosphorylating activity of pure human deoxycytidine kinase: stabilization of different forms of the enzyme by substrates and biological detergents. Paper-6834734. Among the substrates tested, the antitumour drugs gemcitabine and cladribine were bound very tightly by dCK, yielding Kd values of 0.75 and 0.8 microM, respectively, in the presence of UTP. Paper-10871441. The cytotoxicity of dFdC could be competitively reversed by deoxycytidine further suggesting that dFdC, like ara-C, required phosphorylation by deoxycytidine kinase for biological activity. Paper-6076576. Our study indicates that deoxycytidine kinase is a dimer with two subunits and has phosphorylating activity for deoxyguanosine, deoxyadenosine, cytidine, and cytosine arabinoside. Paper-6305752. Deoxycytidine kinase was eluted as a single peak from DEAE-Sephadex column and also from Sephadex G-100 column indicating a molecular weight of about 60 000; no isoenzymes could be detected. Paper-5105336. These results suggest that genetic variation in DCK influences its activity and expression and may predict the variability observed in intracellular levels of the ara-C active metabolite ara-CTP. Paper-12544285. MDL 101,731 showed low activity against murine lymphocytic leukemia P388R cells ( Ara-C-resistant cells) which contained lower deoxycytidine kinase activity than parental P388 cells. Paper-1335760. Both in vitro studies and ex vivo studies have confirmed the ability of the purine analogues to enhance ara-CTP accumulation within leukemic cells via the stimulation of deoxycytidine kinase. Paper-8877103. Oligonucleotides incorporating multiple residues of dC* were immobilized on 15 nm gold nanoparticles and are able to aggregate into i-motif structures even at non-optimal pH values. Paper-12637906. Three major activities were resolved by ion exchange and affinity chromatography: deoxyguanosine- deoxycytidine kinase, deoxycytidine-deoxyadenosine kinase, and adenosine-deoxyadenosine kinase. Paper-4505526. Electrophoretic analysis of thymidine kinase-, deoxycytidine kinase-, and ACV-phosphorylating activities from both untreated and iododeoxyuridine-treated cell extracts displayed identical properties. Paper-4478080. We conclude that cellular resistance to the toxicity of 1-beta-D-arabinofuranosylcytosine and dideoxycytidine in these cell lines is mediated by specific mutations within the dCK gene. Paper-7342754. 5' nucleotidase activity was strongly increased and deoxycytidine kinase activity was moderately reduced in all of the resistant variants, resulting in reduced accumulation of triphosphate analogues. Paper-1956175. In spite of the fact that more than one mechanism can contribute to a cladribine resistance phenotype, a reduction in dCK activity is probably the major determinant of cladribine resistance. Paper-10201911. Analysis of DNA methylation of the 5' region of the deoxycytidine kinase gene in CCRF-CEM-sensitive and cladribine (CdA)- and 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine (CAFdA)-resistant cells. Paper-1564038. In this study, the 5'-flanking region, 7 exons and their flanking introns of DCK were comprehensively screened for genetic variations in 256 Japanese cancer patients administered gemcitabine. Paper-13064316. Other partners of the intracellular metabolism of gemcitabine in relation to the cell cycle effects and DNA repair could be more responsible for the radiosensitising effect than dCK activity. Paper-12069381. Human monoblastoid cells (U937) grown in the presence of therapeutically relevant dideoxycytidine concentrations (0.1 microM) become resistant to the drug thanks to an altered deoxycytidine kinase. Paper-9327354. In summary, pretreatment levels of dCK protein are most correlated with overall survival following gemcitabine treatment and are stable even after resistance to gemcitabine is clinically documented. Paper-11824039. CdA toxicity was proposed to be linked with phosphorylation by deoxycytidine-kinase (E.C. 2.7.1.74), the levels of which have been found to be high in lymphocytes, but low in granulocytes. Paper-7032446. Regarding cytosine analogues, human deoxycytidine kinase was found to be able to phosphorylate both enantiomers with comparable efficiency but only the d-stereoisomer was active in human cell culture. Paper-10509768. These data support the notion that HuR is a key mediator of gemcitabine efficacy in cancer cells, at least in part through its ability to regulate dCK levels posttranscriptionally. Paper-13814176. 3'-OMe-dC was a superior inhibitor of dCK to its 5'-O-methyl congener, consistent with possible participation of the oxygen of the (3')-OH or (3')-OMe as proton acceptor in hydrogen bonding with the enzyme. Paper-8340762. A critical role for uridine nucleotides in the regulation of deoxycytidine kinase and the concentration dependence of 1-beta-D-arabinofuranosylcytosine phosphorylation in human leukemia cells. Paper-6973385. Experiments with a deoxycytidine kinase-deficient mutant CEM T cell line showed that this enzyme was necessary for the phosphorylation and anti-HIV activity of the 2-chloro-2',3'-dideoxyadenosine. Paper-6006419. Deoxyadenosine phosphorylation by deoxycytidine kinase was strongly inhibited by dCTP, but the phosphorylation by T-lymphoblast-specific nucleoside kinase was only weakly inhibited by dCTP. Paper-4479518. The distribution of dCK in cells and tissues has previously been determined by activity measurements, which may be unreliable because of the presence of other enzymes with overlapping substrate specificities. Paper-208674. The level of dCK activity is especially important in chemotherapy with the use of deoxynucleoside analogues like arabinosyl cytosine (Citarabid, ara-C), or 2-chloro-deoxyadenosine ( Cladribine, CdA). Paper-9099237. These results indicate that rSNP haplotypes of dCK gene may serve as a genetic marker for predicting drug responsiveness, which will be beneficial in establishing more effective AML chemotherapeutic regimens. Paper-10849808. Based on these studies, we suggest that the CdA toxicity on CFU-E is mainly mediated by phosphorylation by deoxycytidine kinase, whereas additional mechanisms may be operative in BFU-E and CFU-GM. Paper-7583861. Deoxycytidine kinase and deoxycytidine deaminase values correspond closely to clinical response to cytosine arabinoside remission induction therapy in patients with acute myelogenous leukemia. Paper-5509702. Long-term incubations demonstrated that CdA and APC not only stimulated but also sustained deoxycytidine kinase activity in the cellular context, as compared to the control and BAPTA-AM treated enzyme activities. Paper-10871444. The decreased rate of accumulation of products of dCK in intact cells containing 110 microM ara-CTP suggests that this active triphosphate may limit its own synthesis and phosphorylation of other substrates. Paper-5874316. The role of HuR in gemcitabine efficacy in pancreatic cancer: HuR Up-regulates the expression of the gemcitabine metabolizing enzyme deoxycytidine kinase. Paper-13814176. The RL-G cell line was produced by continuous exposure to gemcitabine and displayed low dCK mRNA and protein expression that conferred resistance both to ara-C (2,250-fold) and to gemcitabine (2,092-fold). Paper-10034354. On the basis of the presence of a single point mutation and a marked reduction in dCK mRNA in this cell line, we postulate that the second allele either is not expressed or is expressed at extremely low levels. Paper-7342754. The effect of 2-chlorodeoxyadenosine was prevented by addition of dipyridamole, a strong nucleoside transport inhibitor, or of deoxycytidine, previously shown to compete for uptake by deoxycytidine kinase. Paper-387515. The Km values of T-lymphoblast-specific nucleoside kinase for deoxyadenosine and deoxyguanosine, 15 and 26 microM, respectively, were smaller than those of deoxycytidine kinase, 150 and 330 microM, respectively. Paper-4479518. The relation between activity and mRNA levels was studied by short interfering RNA (siRNA) method, which showed that in the siRNA treated cells the down-regulation of dCK expression, and activity followed each other. Paper-10847043. 1-beta-d-Arabinofuranosylcytosine (ara-C), a chemotherapy agent often used in combination with MTX, is a nucleoside analog whose incorporation into chromosome requires prior phosphorylation by dCK. Paper-12283944. Deoxyguanosine, deoxyadenosine, and cytidine phosphorylating activities copurified with deoxycytidine kinase to final specific activities of 7.2, 13.5, and 4 mumol min-1 (mg of protein)-1, respectively. Paper-6305752. Phosphorylation of CdA by deoxycytidine kinase and intracellular accumulation of 2-chloro-2'-deoxyadenosine triphosphate (CdATP) were similar in EHEB cells and in other CdA-sensitive cell lines. Paper-8911448. When labeling intensity was compared with survival, low dCK expression (1+ labeling) was correlated with both overall survival (P < 0.009) and progression-free survival following gemcitabine treatment (P < 0.04). Paper-11824039. In accord with these 3D-QSAR models, 15 new DCK analogs with polar functional groups at the 3-position were subsequently designed, synthesized, and evaluated against HIV-1 replication in H9 and MT4 cell lines. Paper-11512274. Down-regulation of deoxycytidine kinase in human leukemic cell lines resistant to cladribine and clofarabine and increased ribonucleotide reductase activity contributes to fludarabine resistance. Paper-9775126. These investigations suggest that cell phenotypes with distinct features can be generated after HDara-C treatment and that decreased deoxycytidine kinase activity appears to be one of the major mechanisms of resistance. Paper-6321080. Denaturing Western blots of extracts from lymphocytes incubated with 2-chlorodeoxyadenosine, aphidicolin and/or BAPTA-AM clearly demonstrated that dCK protein levels were unchanged during these treatments. Paper-10406182. Deoxycytidine kinase, purified from human leukemic spleen to apparent homogeneity, is a multisubstrate enzyme that also phosphorylates purine deoxyribonucleosides [Bohman & Eriksson (1988) Biochemistry 27, 4258-4265]. Paper-6834734. When deoxycytidine ( dC) and cumene hydroperoxide (CuOOH), a tumor promoter and a methyl radical producer, were reacted in the presence of ferrous ion at pH 7.4, the formation of m(5)dC was observed. Paper-13837535. In order to define the relevance of this mechanism in vivo, we analyzed the dCK gene in 16 adult patients with relapsed/refractory acute myeloid leukemia (AML) and clinical resistance to standard-dose and/or high-dose ara-C. Paper-8226541. This deoxyguanosine- deoxycytidine kinase had an apparent molecular weight of 54,000, a Stokes radius of 31 A, and apparent Km values of 10, 130, and 14 microM for deoxyguanosine, deoxycytidine, and ATP, respectively. Paper-4505526. A study of the influence of newly synthesized acyclonucleosides and 1,2,3,4-tetrahydroisoquinoline derivatives on deoxythymidine and deoxycytidine kinase activities in human neurofibrosarcoma and ovarian cancer. Paper-10185148. We have tested this hypothesis by infecting three tumor cell lines, MCF-7, HT-29, and H1437, with the retroviral vector LNPO containing either dCK or LacZ cDNA and measuring the corresponding sensitivity to nucleoside analogues. Paper-543145. 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. Paper-6167882. We confirm that dCK is expressed constitutively and predominantly in lymphoid cells, but conclude that a significant expression may be found in non-lymphoid tissues as well, with increased levels in the corresponding tumor tissue. Paper-7988697. Circular Dichroism studies in the aromatic and far-ultraviolet range and UV difference spectroscopy indicated that binding of substrates to dCK reduced its alpha-helical content and perturbed tryptophan and tyrosine. Paper-10025456. However, T-lymphoblast cell extracts showed a nucleoside kinase activity which phosphorylates deoxycytidine, deoxyadenosine and deoxyguanosine, similar to deoxycytidine kinase, in addition to the three nucleoside kinases. Paper-4479518. Transfection of alternatively spliced dCK forms into AraC-sensitive KA cells, as well as in human leukemic U937 cells and in phytohemagglutinin-stimulated T cells, did not significantly change sensitivity toward AraC. Paper-9370376. 3',4'-Di-O-(-)-camphanoyl-(+)-cis-khellactone ( DCK) is a synthetic khellactone ester that exhibits potent in vitro anti-human immunodeficiency virus ( HIV) activity with a mechanism distinct from clinically used anti-HIV agents. Paper-11535336. While neither 3H-Ara-C uptake, nor intracellular Ara-CTP concentration, TK nor DCK activity were predictive for response, a high 3H-TdR incorporation and a high poly alpha activity were associated with adequate blast cell reduction. Paper-411629. Four 4-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs (7a-d) with different alkyl substituents at the 2'-position were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. Paper-10853829. We have developed a continuous spectrophotometric assay for thymidine and deoxycytidine kinase activities by coupling nucleoside 5'-monophosphate formation to a methylation reaction which generates a product absorbing at 340 nm. Paper-1717985. The nucleoside analogs phosphorylated by dCK in the mitochondria were predominantly incorporated into mitochondrial DNA, whereas the nucleoside analogs phosphorylated in the nucleus or cytosol were incorporated into nuclear DNA. Paper-8380420. In contrast, a CHO mutant deficient in deoxycytidine kinase, and thus unable to accumulate dFdCTP, maintained its CTP pools under identical conditions, suggesting that the CTP pool depletion was dependent on dFdC phosphorylation. Paper-386067. Here, we show that stimulation of deoxycytidine kinase by UV-light also is calcium-dependent and pifithrin-alpha-sensitive in tonsillar lymphocytes, while thymidine kinase 1 activity is stabilised in the presence of BAPTA-AM. Paper-12290094. The chemical diversification of DNA precursors was undertaken in Escherichia coli by expressing the human gene for deoxycytidine kinase, and supplying such recombinant strains with nucleoside analogues bearing an altered base or sugar. Paper-1043706. A small part (5 to 10%) of the loaded ACV-phosphorylating activity seemed to migrate with the deoxycytidine kinase activity from cytosol. dTTP and dCTP, at relatively high concentrations, partially inhibited ACV-phosphorylating activity. Paper-4478080. 2-Chlorodeoxyadenosine ( CdA), an antileukemic agent used in treatment of hairy cell leukemia and chronic lymphocytic leukemias (B-CLL), is phosphorylated by dCK which was used as the selective substrate for this enzyme. Paper-7988697. We screened 5378 bp sequences of the dCK gene, including all exons and the 5' flanking region, and identified two single nucleotide polymorphisms ( SNPs) in the regulatory region (rSNPs) with high allele frequencies. Paper-10849808. Binding of nucleosides had no effect on the pyrene fluorescence of Cys-185-Ala dCK, indicating that the conformational changes observed upon substrate binding to wild-type dCK-PM involved the "lid region" of which Cys 185 is a part. Paper-11802683. It turned out that only 2'-deoxythymidine-5'-thiosulphate (dThd-5'-TS) can potentiate the dCK activity, without influencing the thymidine kinase isoenzymes during short-time treatments of human peripheral blood and tonsillar lymphocytes. Paper-9743105. RESULTS: Both retroviral and adenoviral vector-mediated transduction of the dCK complementary DNA resulted in marked sensitization of tongue squamous carcinoma cell lines to the cytotoxic effects of cytarabine in vitro. Paper-9479510. These studies show that administration of dThd or HU in conjunction with high concentrations of Ara-C results in an enhanced antiproliferative effect of Ara-C against Ara-C-resistant leukemic cells deficient in deoxycytidine kinase. Paper-7013561. Suramin also suppressed the increase in DNA repair synthesis elicited by UV-C irradiation, suggesting that upregulation of dCK activity could contribute to the normal completion of DNA repair synthesis elicited by UV light. Paper-9743106. Deoxycytidine kinase (NTP:deoxycytidine 5'-phosphotransferase, EC 2.7.1.74) is an enzyme that catalyzes phosphorylation of deoxyribonucleosides and a number of nucleoside analogs that are important in antiviral and cancer chemotherapy. Paper-80691. Although L-Fd4C is converted intracellularly by cytoplasmic deoxycytidine kinase to its mono-, di- and triphosphate metabolites,43 the newly prepared bis(SATE)-L-Fd4CMP proved to be more potent against HBV yet less cytotoxic than L-Fd4C itself. Paper-9439511. Site-directed mutagenesis and use of an anti-phospho-Ser-74 antibody demonstrated that Ser-74 phosphorylation was crucial for dCK activity in HEK 293T cells, whereas phosphorylation of other identified sites did not seem essential. Paper-11317053. Structural studies of ternary complexes of human dCK show that the enzyme conformation adjusts to the different hydrogen-bonding properties between dA and dG and to the presence of substituent at the 2-position present in dG and cladribine. Paper-12933481. In this study, stopped-flow experiments were used to monitor intrinsic fluorescence changes induced upon binding of various phosphate donors (ATP, UTP, and the nonhydrolyzable analogue AMP-PNP) and the acceptor dCyd to recombinant dCK. Paper-1909332. To understand the molecular basis for the nonenantioselectivity of dCK, we solved the crystal structures of the enzyme in complex with the L-enantiomer and of its physiological substrate deoxycytidine and with the L-nucleoside analogue FTC. Paper-13309865. Here, we demonstrate an approach to detecting DCK activity in vivo by using positron emission tomography (PET) and (18)F-labeled 1-(2'-deoxy-2'-fluoroarabinofuranosyl) cytosine] ([(18)F]FAC), a PET probe recently developed by our group. Paper-13631913. Human dCK catalysed the phosphorylation of D- and L-enantiomers of beta-dA, beta-araA, and beta-dG with enantioselectivities favoring the unnatural enantiomer for the adenosine derivatives and the natural enantiomer for 2'-deoxyguanosine. Paper-2081613. Though deoxycytidine kinase activity in cell extracts was unaltered or increased after treatment failure, the activity in situ, measured as the rate of 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP) formation, was decreased. Paper-6794492. Here, we show that deoxyadenosine itself is also a potent activator of dCK if its deamination was prevented by the adenosine deaminase inhibitor deoxycoformycin. Paper-11286292. At low concentrations (less than 25 mumol/L) of deoxyadenosine or ara-adenine, deoxycytidine kinase deficiency decreases growth sensitivity of human T-lymphoblasts to deoxyadenosine approximately fourfold, and to ara-adenine approximately twofold. Paper-4775963. Because the levels of deoxynucleotide pools and the activity of deoxycytidine kinase are cell cycle-specific, we investigated the effect of cell cycle phases on the accumulation of ara-CTP and the influence of F-ara-A pretreatment on such accumulation. Paper-7382159. Specifically, we hypothesized that steric repulsion between the methyl group of the thymine base and Arg104 is the main factor preventing the phosphorylation of thymidine by wild-type dCK. Paper-13853077. A number of genotoxic and antiproliferative agents such as 2-chlorodeoxyadenosine ( Cladribine; CdA) and aphidicolin (APC) have been shown to stimulate the activity of deoxycytidine kinase, the main deoxynucleoside salvage enzyme in lymphocytes. Paper-10871444. Based on the structures and biodata of previous DCK analogs, 3D-QSAR studies have been performed which resulted in two reliable computational models, CoMFA and CoMSIA, with r(2) values of 0.995 and 0.987, and q(2) values of 0.662 and 0.657, respectively. Paper-11512274. To evaluate the possibility that diminished deoxycytidine kinase was a mechanism of drug resistance, the relative area under the concentration X time curve ( AUC) of the active triphosphate of each prodrug in the CLB of individuals was compared. Paper-5678417. Southern blot analysis using genomic DNA from peripheral blood or bone marrow samples containing > or = 70% leukemic blasts and agarose gel electrophoresis of cDNA obtained by RT-PCR did not reveal gross rearrangements of the dCK gene. Paper-8226541. A series of analogues of L-adenosine and of L-guanosine, including beta-L-dA, beta-L-Ado, beta-L-araA, and beta-L-dG, have been shown to be substrates of human deoxycytidine kinase thus demonstrating the complete lack of enantioselectivity of this enzyme. Paper-1945816. Steady-state fluorescence demonstrated that deoxycytidine (the phosphate acceptor) and ATP (the phosphate donor) bound to different sites on dCK and fluorescence quenching revealed bimodal binding of deoxycytidine and unimodal binding of ATP. Paper-10025456. Once inside the cell gemcitabine is rapidly phosphorylated by deoxycytidine kinase, the rate-limiting enzyme for the formation of the active metabolites gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate ( dFdCTP). Paper-664415. Moreover, real-time quantitative reverse transcriptase-polymerase chain reaction showed that patients with -360CG/-201CT and -360GG/-201TT genotypes expressed higher level of dCK mRNA compared to those with the -360CC/-201CC genotype (P = 0.0034). Paper-10849808. We sequenced 1.5 kilobases of the DCK proximal promoter and all seven coding exons in International HapMap Project panels (n = 90 each) with European (Centre d' Etude du Polymorphisme Humain; CEPH) or African (Yoruba people in Ibadan, Nigeria; YRI) ancestry. Paper-12544285. To determine the factors that limit the phosphorylation efficiency of the prodrug, we solved the crystal structure of dCK to a resolution of 1.6 A in complex with its physiological substrate deoxycytidine and with the prodrugs AraC and gemcitabine. Paper-9757552. The level of intracellular Ara-C accumulation and Ara-CTP formation was far more important in Reh cells than in myeloid cell lines but was not closely related to deoxycytidine kinase activity or to deoxycytidine triphosphate pool size. Paper-6465037. In order to determine whether lack of dCK affected the formation of the active triphosphate of the deoxycytidine analog dFdC, dFdCTP accumulation and retention was measured in H9 parental and AZT-resistant cells after exposure to 1 and 10 microM dFdC. Paper-9513359. The growth inhibitory effects and metabolism of 2',3'-dideoxycytidine (ddC) were examined in wild type human CEM T lymphoblasts and in mutant populations of CEM cells that were genetically deficient in either nucleoside transport or deoxycytidine kinase activity. Paper-6251660. We determined the average distances between PM-labeled Cys residues and Trp residues in dCK in the absence and presence of various pyrimidine and purine nucleoside analogues with the Trp residues as energy donors and PM-labeled Cys residues as acceptors. Paper-11802683. Deoxycytidine kinase from Ehrlich carcinoma cells was purified 10400-fold by ammonium sulfate fractionation and affinity chromatography using Sepharose 4B coupled to 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosyl-N4-palmitoylcytosine , with a yield of 45%. Paper-1770253. CONCLUSIONS: These data demonstrate that the gemcitabine and pemetrexed combination displays schedule-dependent synergistic cytotoxic activity, favorably modulates cell cycle, induces apoptosis, and enhances dCK expression in pancreatic cancer cells. Paper-10413329. A deoxycytidine kinase-deficient variant of HL60 cells (HL60-araC), isolated by its resistance to 1-beta-D-arabinofuranosyl cytosine (ara-C), shows cross-resistance to the differentiation-inducing and growth-inhibitory effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Paper-74191. Furthermore, topotecan treatment significantly decreased the amount of the activated form of Akt, and enhanced the expression of dCK (+155.0 and +115.3% in A549 and Calu-6 cells, respectively), potentially facilitating gemcitabine activity. Paper-10805412. The HL60/CdA cells showed cross-resistance to 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine, Fara-A, arabinofuranosyl cytosine, difluorodeoxyguanosine, and difluorodeoxycytidine toxicity, most likely because of the decreased phosphorylation of these analogues by dCK. Paper-2052000. Conclusions: These results show that genetic modifications in non-hematological malignant cells may be associated with resistance to gemcitabine, and that the gene transfer of non-human genes can be used for the reversion of nucleoside analogue resistance due to dCK deficiency. Paper-12055316. All other examined beta-L-cytidine analogs, [1-beta-L-lyxofuranosyl cytosine (beta-L-lyxoC), l-beta-L-xylofuranosyl cytosine (beta-L-xyloC), and 5-fluoro-1-beta-L-xylofuranosyl cytosine (beta-L-Fxylo C)], were substrates of dCK regardless of the nature of the pentose. Paper-1616845. Therefore we have measured dCK polypeptide levels in extracts of normal and malignant human peripheral blood mononuclear cells, gastrointestinal tissues and sarcomas, using a specific immunoblotting technique, as well as the phosphorylation of CdA in the same extracts. Paper-208674. 2',3'-Dideoxycytidine (ddCyd) is a prescription anti-retroviral drug that causes mitochondrial toxicity and peripheral neuropathy. ddCyd is actively phosphorylated by cytosolic deoxycytidine kinase and nucleoside (di)phosphate kinase to the 5'-triphosphate derivative. Paper-2131788. Substrate activities of cytosine nucleosides vs dCK were as follows: 2'-fluoro-dC > 2'-O-methyl-C > araC > 2'-fluoro-2'-deoxy-araC > 3'-O-methyl-dC = 3'-fluoro-2',3'-ddC > cytosine beta-L-riboside > 2',3'-ddC > C = 1-(4-hydroxy-1,2,-butadienyl)-cytosine (cytalene) = 2'-azido-dC. Paper-1483972. After purification of 32P-labeled dCK, digestion by trypsin, and analysis of the radioactive peptides by tandem mass spectrometry, the following four in vivo phosphorylation sites were identified: Thr-3, Ser-11, Ser-15, and Ser-74, the latter being the major phosphorylation site. Paper-11317053. Studies using purified deoxycytidine kinase support the conclusion that the increase in plasma levels of F-ara-A is in part the result of an effective competition by ara-C for phosphorylation by this enzyme, leading to a perturbation of the pharmacokinetics of intracellular F-ara-ATP. Paper-7386349. 3-Methyl- (7), 4-methyl- (8), and 5-methyl- (9) 3',4'-di-O-(S)-camphanoyl-(3'R, 4'R)-(+)-cis-khellactone showed EC(50) and therapeutic index values of <5.25 x 10(-5) microM and >2.15 x 10(6), respectively, in H9 lymphocytes, which are much better than those of DCK and AZT in the same assay. Paper-1921577. As a first step toward improving dideoxynucleoside inhibition of human immunodeficiency virus replication in human lymphocytes, we examined the kinetics of 5'-phosphorylation of a series of 2',3'-dideoxynucleosides, using deoxycytidine kinase purified from human thymus extracts. Paper-5619137. At different times after irradiation, the activities of nine enzymes involved in nucleotide metabolism were measured, the levels of thymidine kinase and deoxycytidine kinase proteins were evaluated by Western blot, and cell-cycle kinetics were analysed by flow cytometry. Paper-1973680. One leiomyosarcoma and one extra-skeletal osteosarcoma showed a dCK levels comparable to those found in normal lymphocytes (84 +/- 6 and 109 +/- 4 ng/mg), while other sarcoma samples contained levels comparable to the gastrointestinal adenocarcinomas (20 +/- 7 ng/mg, n = 12). Paper-7988697. An 80% diminished rate of [3H]ddC influx into the two nucleoside transport-deficient lines could account for their resistance to the ddN, while the resistance of the deoxycytidine kinase deficient cells to ddC toxicity could be explained by a virtually complete failure to incorporate [3H]ddC in situ. Paper-6251660. Dideoxyliponucleotide ( ddCDP-choline and ddCDP-ethanolamine) formation was also much slower (between one-half and one-third as fast) in U937-R than in control cells, although catabolism occurred at similar rates. ddC was phosphorylated by a cytoplasmic deoxycytidine kinase in both cell lines. Paper-420892. However, no significant difference in the intracellular concentration of Ara-C was observed among the cells tested, which indicates that the Ara-C resistant phenotype in our models occurred due to the lower expression and activity of dCK rather than a change in the ability to take up Ara-C. Paper-13665035. We have recently identified a complementary DNA clone which encodes the complete amino acid sequence for 2'-deoxycytidine kinase ( dCK), the enzyme required for the initial phosphorylation of several deoxyribonucleosides and their analogues that are widely used as chemotherapeutic and antiviral agents. Paper-7342754. We attribute this to the ability of cladribine to combine advantageous properties from dA (favorable hydrogen-bonding pattern) and dG (propensity to bind to the enzyme in its anti conformation), suggesting that dA analogues with a substituent at the 2-position are likely to be better activated by human dCK. Paper-12933481. Recently, a new cytidine analogue, gemcitabine, has shown impressive activity as a single agent against several solid malignancies ( ovarian cancer, non-small cell lung cancer), demonstrating that in solid tumours deoxycytidine kinase can be an important target for the activation of antimetabolites. Paper-8130340. (S,S)-IsoddATP is among the most potent inhibitors of HIV reverse transcriptase known, which suggests that the observed low efficiency of phosphorylation of this compound by dCK is a key factor that limits the capacity of human lymphocytes to make ( S,S)-isoddA an exceptionally active anti-HIV agent. Paper-8624030. One leiomyosarcoma and one extra-skeletal osteosarcoma showed dCK levels comparable with those found in normal lymphocytes (84 +/- 6 and 109 +/- 4 ng/mg, respectively), while other sarcoma samples contained lower levels, comparable to the gastrointestinal adenocarcinomas (20 +/- 7 ng/mg, n = 12). Paper-208674. The naturally resistant colon 38 carcinoma, on the other hand, in addition to a decrease in the activity of its deoxycytidine kinase, showed a lower level of activity of all its purine and pyrimidine kinases, along with a notably elevated nucleoside triphosphatase activity (with ATP as substrate) when compared to P388. Paper-5302247. 3-Methyl, 4-methyl, and 5-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (2-4) all were extremely potent against HIV-1 replication in H9 lymphocyte cells with EC50 and therapeutic index values of < 4.23 x 10(-7) microM and > 3.72 x 10(8), respectively, which are much better than those of DCK and AZT in this assay. Paper-1697375. In this study, expression of dCK mRNA was measured by a competitive template reverse transcriptase polymerase chain reaction (CT RT-PCR) in seven cell lines of different histological origin, 16 childhood and adult AML samples, 10 human liver samples and 11 human liver metastases of colorectal cancer origin. Paper-9668165. These apoptotic phenomena induced by 2CdA were inhibited by cycloheximide ( CHX; a protein synthesis inhibitor), deoxycytidine (dC; a substrate of deoxycytidine kinase), acetyl Ile-Glu-Thr-Asp aldehyde (Ac-IETD-CHO; a caspase-8 inhibitor) and acetyl Asp-Glu-Val-Asp aldehyde ( Ac-DEVD-CHO; a caspase-3 inhibitor). Paper-2114463. Despite dCK activity being by far the highest in cells of lymphoid origin, the effects of FMdC were detectable at the lowest drug concentration only in a solid tumor cell line, and at higher concentrations they were qualitatively similar in the two tumor lines (increased cell protein content, cell cycle block and apoptosis). Paper-8523862. To determine the molecular basis of the kinetically observed phosphoryl donor preference, we solved crystal structures of a dCK variant lacking a flexible insert (residues 65-79) but having similar catalytic properties as wild type, in complex with deoxycytidine (dC) and UDP, and in the presence of dC but the absence of UDP or ADP. Paper-10830659. MATERIALS AND METHODS: The levels of the dCK gene as well as other gemcitabine-related genes (hENT1, RRM1 and RRM2) were analyzed in gemcitabine-resistant pancreatic cancer cells (GR cells) using quantitative real-time reverse transcription polymerase chain reaction. Paper-12920813. Deoxycytidine kinase (dCyd kinase, EC 2.7.1.74) is a key enzyme in the salvage pathway of deoxyribonucleosides, and the human enzyme is a dimer of two 30 kDa polypeptides with a broad substrate specificity, phosphorylating both purine and pyrimidine nucleosides and using various nucleoside triphosphates as phosphate donors. Paper-6836443. Thus, the deoxycytidine kinase gene accumulates mutations at a very high rate, as already reported for other cytidine analogues (i.e. Ara C) suggesting that the design of new antiviral or anticancer drugs of the cytidine family should take into account the potential development of cell resistance as a critical factor in drug failure. Paper-9327354. Cytarabine, pentostatin, fludarabine, cladribine and gemcitabine are all prodrugs whose plasma pharmacokinetics do not fully reflect their therapeutic activity; after cellular uptake, these compounds undergo phosphorylation by deoxycytidine kinase before their incorporation into DNA results in cell death. Paper-8590763. The activities of aspartate transcarbamylase (de novo pyrimidine biosynthesis pathway) and of deoxycytidine kinase as well as deoxycytidine deaminase (salvage pyrimidine biosynthesis pathway) were determined in extracts prepared from 40 brain tumors of different types in comparison with extracts from normal nervous tissues. Paper-5593712. Recent applications have included the use of a fixed-dose rate regimen in patients with advanced pancreatic cancer based on the observation that deoxycytidine kinase is saturated at the plasma gemcitabine concentrations achieved with standard infusion, thereby limiting the accumulation of intracellular gemcitabine triphosphate. Paper-9543538. Furthermore, independent analysis of the individual genes of interest revealed statistically significant differences for risk of disease progression (adjusted hazard ratios [HRs]) with underexpression of dNT-1 (HR = 0.45; P = .042), CD73 (HR = 0.40; P = .022), and dCK (HR = 0.0.48; P = .035), and overexpression of hCNT3 (HR = 4.7; P = .0007) genes. Paper-11016926. To characterize the dCK promoter region and to determine whether it mediates higher levels of gene expression in T lymphoblasts, we have analyzed a 700-bp genomic fragment encompassing 548 bp of 5' flanking region for functional activity and for transcription factor binding using T and B lymphoblast cell lines and nuclear extracts. Paper-194009. The gemcitabine --> topotecan sequence is antagonistic while drug synergism is obtained with the simultaneous and the sequential topotecan --> gemcitabine combinations, which are associated with induction of decreased Akt phosphorylation and increased dCK expression. Paper-10805412. We report that dCK protein expression is expressed in the majority of pancreatic cancers analyzed (40 of 44 cases, 91%) and showed a range of labeling intensities ranging from 1+ (labeling weaker in intensity than normal lymphocytes present in same section) to 3+ (labeling greater in intensity than normal lymphocytes present in same section). Paper-11824039. We have examined the effect of the ribonucleotide reductase inhibitors thymidine (dThd) and hydroxyurea (HU) on the metabolism and cytotoxicity of high concentrations (10 to 100 mumol/L) of cytosine arabinoside ( Ara-C) in a deoxycytidine kinase-deficient, highly Ara-C-resistant human promyelocytic leukemic cell subline (HL-60/ Ara-C). Paper-7013561. A troxacitabine-resistant prostate cancer subline (DU145(R); 6300-fold) that exhibited reduced uptake of troxacitabine was cross-resistant to both gemcitabine (350-fold) and cytarabine (300-fold). dCK activity toward deoxycytidine in DU145(R) cell lysates was <20% of that in DU145 cell lysates, and no activity was detected toward troxacitabine. Paper-8856970. These synonyms are used for gene DCK (deoxycytidine kinase): MGC138632, MGC117410, Deoxycytidine kinase, dCK. These accession numbers are used for gene DCK: Q6FI11 (UNIPROT__AC), Q5TZY7 (UNIPROT__AC), CAG46674 (NCBI_GENBANK__AC), AAI03765 (NCBI_GENBANK__AC). DCK is a homologue of Os05g0430200 (Os05g0430200) from Oryza sativa Japonica Group. DCK is a homologue of DCK (deoxycytidine kinase) from Bos taurus. DCK is a homologue of DCK (deoxycytidine kinase) from Pan troglodytes. DCK is a homologue of DCK (deoxycytidine kinase) from Gallus gallus. DCK is a homologue of DCK (deoxycytidine kinase) from Canis lupus familiaris. DCK is a homologue of Dck (deoxycytidine kinase) from Mus musculus. DCK is a homologue of Dck (deoxycytidine kinase) from Rattus norvegicus. DCK is a homologue of dck (deoxycytidine kinase) from Danio rerio. Important links ! iHOP - Information Hyperlinked over Proteins . Concept & Implementation by Robert Hoffmann.