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. The pI value of TSK ( pH 8.2) is quite different from that of dCK (4.8). Paper-4940729. DCK catalyzes the intracellular phosphorylation of fludarabine. Paper-15735119. The structures reveal the determinants of dCK substrate specificity. Paper-9757552. No other tested L-adenosine or L-guanosine analog was a substrate of dCK. Paper-2081613. The gene expression of dCK (beta-actin ratio) varied between 0.44 and 2.56. Paper-13532107. AIM: To measure dCK expression in tumour cells from different origins. Paper-11034411. 5-Fluorocytosine derivatives as inhibitors of deoxycytidine kinase. Paper-14559195. Sequencing of the dCK coding region showed point mutations in seven patients. Paper-8226541. Thus L-dCTP, like dCTP, could serve as a feedback inhibitor for dCK. Paper-1486188. The p16 and dCK CpG islands were also unmethylated in the 8 AML specimens. Paper-1616974. However, some patients developed drug-resistance due to deficiency in DCK. Paper-15586728. In normal cells the p15, p16 and dCK CpG islands were largely unmethylated. Paper-1616974. 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. Deoxycytidine kinase mRNA expression in childhood acute lymphoblastic leukemia. Paper-1127775. No inhibition of dCK-mediated dCyd phosphorylation was found by either araG or dFdG. Paper-1588939. Pretreatment deoxycytidine kinase levels predict in vivo gemcitabine sensitivity. Paper-9653443. The expression of dCK has been postulated to be correlative of gemcitabine resistance. Paper-11824039. Chiral influences of feedback inhibition with dCTP on murine deoxycytidine kinase. Paper-1486188. 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. These observations demonstrated that dCK phosphorylates CAFdA more efficiently than CdA. Paper-8292174. Feedback inhibition of dCK by deoxycytidine 5'-triphosphate ( dCTP) was also studied. Paper-7778839. We show that [(18)F]FAC is a DCK substrate with an affinity similar to that of dFdC. Paper-13631913. 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. The formation of dUTP from dCyd, was also enhanced by NaF, in parallel of dCK potentiation. Paper-1483935. Elucidation of different binding modes of purine nucleosides to human deoxycytidine kinase. Paper-12933481. This is in line with substrate specificity tests, which revealed a very low affinity of dCK. Paper-1945828. All point mutations detected were nonrandomly distributed within the dck coding region. Paper-273168. Staurosporine also directly increased dCK in cell free extracts. Paper-15143307. Extending thymidine kinase activity to the catalytic repertoire of human deoxycytidine kinase. Paper-13853077. This study found novel DCK polymorphisms, including nonsynonymous SNPs, in exons 3 and 6. Paper-12154100. 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. Identification of residues involved in the substrate specificity of human and murine dCK. Paper-9263894. Direct photoaffinity-labelling of human deoxycytidine kinase with the feedback inhibitor dCTP. Paper-6836443. Intracellular phosphorylation of dCK on Ser-74 results in increased nucleoside kinase activity. Paper-14285748. Retroviral transfer of deoxycytidine kinase into tumor cell lines enhances nucleoside toxicity. Paper-543145. In the cell line panel, the range was 2.97-56.9 (x10(-3)xdCK/beta-actin) of dCK mRNA expression. Paper-9668165. Deoxycytidine (CdR) and dFdC had Km values of 1.5 and 4.6 microM for dCK, respectively. Paper-7778839. As a purine-nucleoside analog, clofarabine is a better substrate of dCK than deoxycytidine. Paper-10824771. The enzyme activity in liver metastases was correlated to dCK mRNA expression (r=0.497, P=0.05). Paper-9668165. This indicates that dCK might be an important prognostic marker for gemcitabine sensitivity. Paper-9653443. The decreased expression of dCK also resulted in lower activity in both Ara-C resistant variants. Paper-13665035. Two specific inhibitors of the MAPK/ERK pathway, PD-98059 and U-0126, also enhanced dCK activity. Paper-10299789. We show that several hydrophobic residues at position 104 endow dCK with thymidine kinase activity. Paper-13853077. TK and dCK levels in PBMC from HIV infected and non infected children did not significantly differ. Paper-14635989. The phosphorylation of CdA in crude extracts showed a close correlation to the dCK polypeptide level. Paper-208674. To further unravel its regulation, dCK was overexpressed in HEK-293 cells as a His-tag fusion protein. Paper-10871446. G-phase lymphocytes showed a higher sensitivity for dCK stimulation than S-phase cells. Paper-2112488. A model for dCK was used to try to explain the functional role of these amino acid substitutions. Paper-9263894. Defective expression of deoxycytidine kinase in cytarabine-resistant acute myeloid leukemia cells. Paper-13665035. The longest open reading frame encoded a protein that was 48% identical to dCK at the amino acid level. Paper-602918. Thus, L-dCTP was shown to be capable of serving as a feedback inhibitor for dCK instead of D-dCTP. Paper-1216419. Of the purine analogs tested as substrates for dCK, only CdA could compete with 2'-deoxycytidine (dCyd). Paper-1588939. SiRNA-transfected cells reduced in dCK activity were 3- to 6-fold less sensitive to CdA, AraC, and CAFdA. Paper-12870294. Like dCK, thymidine kinase 2 (TK2) catalyzes the initial step of the phosphorylation of dcyd to dCTP. Paper-312363. Methylation specific PCR to characterize methylation of the promoter of deoxycytidine kinase. Paper-15256856. In two patients we showed by enzymatic analysis that the drug-resistance was due to deficiency in DCK. Paper-15586728. METHODS: Seven SNPs in the dCK gene were sequenced in six human pancreatic cancer cell lines. Paper-15712742. These inhibitory effects of L-dCTP on dCK were similar to the results of earlier studies using D-dCTP. Paper-1216419. CONCLUSION: dCK mRNA expression is a candidate indicator for GEM efficacy in unresectable pancreatic cancer. Paper-13870537. Systematic exploration of active site mutations on human deoxycytidine kinase substrate specificity. Paper-14323871. Here, the functional involvement of dCK in gemcitabine-resistance of pancreatic cancer was investigated. Paper-12920813. These results indicate that the dFdCyd resistance phenotype is stable, and mainly due to dCK deficiency. Paper-8011166. The stimulation of dCK activity in cells was accompanied by an imbalance in the dThd and dCyd metabolism. Paper-9743105. Activation of deoxycytidine kinase by UV-C-irradiation in chronic lymphocytic leukemia B-lymphocytes. Paper-9743106. In addition, dCK activity and mean mRNA levels were 2.5-fold higher in the metastases than in the liver samples. Paper-9668165. Recently, crystal structures of dCK (dCKc) with various pyrimidine nucleosides as substrates have been reported. Paper-11298743. These results indicate that the gemcitabine resistance phenotype is stable and mainly due to dCK deficiency. Paper-386069. The reaction depended on inorganic phosphate, and dCK showed maximum cleavage activity between pH 7 and pH 8. Paper-10563676. Is the resistance of gemcitabine for pancreatic cancer settled only by overexpression of deoxycytidine kinase? Paper-14196764. Our analysis suggests that dCK would phosphorylate acyclic guanine analogues if they can induce a similar rotation. Paper-15332440. Current assays to measure DCK expression and activity require biopsy samples and are prone to sampling errors. Paper-13631913. Transient transfection experiments indicated that the truncated dCK transcripts are not translated to protein. Paper-10509757. Activation of deoxycytidine kinase by gamma-irradiation and inactivation by hyperosmotic shock in human lymphocytes. Paper-9740656. Deoxycytidine kinase expression and activity in patients with resistant versus sensitive acute myeloid leukemia. Paper-9571294. The observation that purified dCK phosphorylates S2242 to its monophosphate further corroborates these results. Paper-1311948. In a parallel set of experiments 1 mM deoxycytidine was added to prevent phosphorylation of the drug by dCK. Paper-2082975. The lymph node (LN) ratio and dCK protein expression were significant predictors of DFS and OS in univariate analysis. Paper-15496505. Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer. Paper-12920813. The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation. Paper-10824771. Pyrimidine salvage enzymes in human tonsil lymphocytes: II. Purification and properties of deoxycytidine kinase. Paper-5105336. 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. The dCK-targeting siRNA significantly reduced gemcitabine sensitivity (p < 0.01) without affecting cell proliferation. Paper-12920813. Enhancement of dCK activity could also be achieved with the topoisomerase II inhibitor, etoposide. Paper-2112488. No correlations were found between TK or dCK activities and plasma viral load, CD4 cell count, sex or age of patients. Paper-11003703. The structure reveals that while ACV does bind at the dCK active site, it does so adopting a nonproductive conformation. Paper-15332440. Thymidine kinase and deoxycytidine kinase activity in mononuclear cells from antiretroviral-naive HIV-infected patients. Paper-11003703. L-dCTP inhibited dCK non-competitively with 2'-deoxycytidine (D-dCyd) and competitively with phosphate donor D-ATP. Paper-1216419. Activation of deoxycytidine kinase by protein kinase inhibitors and okadaic acid in leukemic cells. Paper-10299789. Study of the efficacy of a pronucleotide of 2-chloro-2'-deoxyadenosine in deoxycytidine kinase-deficient lymphoma cells. Paper-14731485. In this study, when the CD-transduced cells were also transduced with dCK they became relatively more sensitive to dFdC. Paper-9482128. Thymidine is phosphorylated by both thymidine kinases, and deoxycytidine is phosphorylated by both dCK and TK2. Paper-7217313. Selective increase of dATP pools upon activation of deoxycytidine kinase in lymphocytes: implications in apoptosis. Paper-10615271. 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. Furthermore, homology of the peptide sequences od dCK to parts of thymidine kinases and protein-tyrosine kinases are detected. Paper-6966857. The dCK A9846G SNP may act as a genetic marker to predict chemotherapy efficacy of gemcitabine in pancreatic cancer. Paper-15712742. However, the association between SNPs in the dCK gene and chemosensitivity to gemcitabine has not been fully established. Paper-15712742. The CdA and CAFdA resistant cell lines exhibited increased resistance to the other nucleoside analogues activated by dCK. Paper-9775126. Enhancement of cytarabine sensitivity in squamous cell carcinoma cell line transfected with deoxycytidine kinase. Paper-9479510. RESULTS: The genotype of the A9846G SNP in the dCK gene was determined in six human pancreatic cancer cell lines. Paper-15712742. Identification of in vivo phosphorylation sites on human deoxycytidine kinase. Role of Ser-74 in the control of enzyme activity. Paper-11317053. Relationship of deoxycytidine kinase and cytoplasmic 5'-nucleotidase to the chemotherapeutic efficacy of 2-chlorodeoxyadenosine. Paper-7582998. Increased ratio between deoxycytidine kinase and thymidine kinase 2 in CLL lymphocytes compared to normal lymphocytes. Paper-312363. 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. 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. Expression of deoxycytidine kinase in leukaemic cells compared with solid tumour cell lines, liver metastases and normal liver. Paper-9668165. In the current study, the crystal structure of clofarabine- and ADP-bound dCK was solved to 2.55 angstroms by molecular replacement. Paper-10824771. DCK expression in cultured lymphoblast cell lines is not solely a function of the T or B lineage derivation. Paper-194009. Recently, activation of dCK has been considered as a protective cellular response to a number of DNA-damaging agents in lymphocytes. Paper-10406182. For many of these compounds, the phosphorylation step catalyzed by dCK is the rate-limiting step in their overall activation pathway. Paper-9757552. AraC induced both rearrangements and point mutations in the dck gene when administered over 140 days and 180 days, respectively. Paper-273168. Deoxyguanosine-phosphorylating activity eluted as a single peak in association with deoxycytidine kinase. Paper-4505526. We also established an in vitro model of Ara-C resistance using phosphorothioate antisense oligonucleotides to dCK (dCK-AS). Paper-8388377. When cells were gamma-irradiated in the presence of calyculin A, a more pronounced activation of dCK was observed. Paper-9740656. Cell survival, inhibition of DNA synthetic capacity (DSC), ara-CTP anabolism, and dCk enzymatic characteristics were studied. Paper-147555. Immunocytochemical detection of deoxycytidine kinase in pediatric malignancies in relation to in vitro cytarabine sensitivity. Paper-10615272. After in vitro transcription-translation dCK proteins are analyzed for their molecular weight and phosphorylating capacities. Paper-8385325. Therefore, we crystallized dCK in complex with ACV at the nucleoside phosphoryl acceptor site and UDP at the phosphoryl donor site. Paper-15332440. In addition, we observed that dFdU, the deaminated form of dFdC, was cytotoxic to the A-549- dCK cells, but not the wild-type cells. Paper-9482128. Structural analysis of the deoxycytidine kinase gene in patients with acute myeloid leukemia and resistance to cytosine arabinoside. Paper-8226541. The results showed that an inter-individual variability in TK and dCK activities does exist in both HIV infected and uninfected children. Paper-14635989. The interactions between 2-Cl and its surrounding hydrophobic residues contribute to the high catalytic efficiency of dCK for clofarabine. Paper-10824771. Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients. Paper-10849808. 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. 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. A dose-dependent inhibition of dCK was observed, highlighting this kinase as a possible additional secondary molecular target for imatinib. Paper-11093813. A histological examination revealed infiltration of eosinophils into the dCK gene-transduced but not into parental Colon 26 tumor. Paper-8378920. Here, the structures of dCK complexes with the products dCMP, UDP and Mg2+ ion, and with dAMP, UDP and Mg2+ ion are reported. Paper-12644112. An apparent Km of 13 microM for deoxycytidine and Ki of 55 microM for arabinosyl-cytosine were found for the tonsillar deoxycytidine kinase. Paper-5105336. This catalytic activity is important for the design of in vitro experiments with dCK, such as crystallization and NMR spectroscopy. Paper-10563676. 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. In bladder tumors a similar correlation was found, while esophageal tumors with a high dCK expression responded to gemcitabine treatment. Paper-10531061. The ratio of dCK to 5'-NT activity was significantly increased in bryostatin 1 treated WSU-CLL cells after 48 h. Paper-1675580. 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. Gemcitabine exposure to pancreatic cancer cells enriches the association between HuR and dCK mRNA and increases cytoplasmic HuR levels. Paper-13814176. Activation of deoxycytidine kinase in lymphocytes is calcium dependent and involves a conformational change detectable by native immunostaining. Paper-10406182. Activation of deoxycytidine kinase during inhibition of DNA synthesis by 2-chloro-2'-deoxyadenosine ( Cladribine) in human lymphocytes. Paper-1616837. Treatment of normal and malignant cells with nucleoside analogues and etoposide enhances deoxycytidine kinase activity. Paper-2112488. 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. Neither the dCK activity nor the polypeptide correlates with the S phase of the cells, as thymidine kinase (TK1) does in tonsils. Paper-932565. METHODS AND MATERIALS: All seven DCK exons and the promoter region were sequenced from 100 healthy volunteers (79 females and 21 males). Paper-12154100. Thus, the ratio of dCK (specific for cladribine) to high-Km 5'-NT activity in R13 and R23 was reduced to 65.3% and 63.7%, respectively. Paper-1660694. 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. We report the sequence of the putative TK of channel catfish virus, a herpesvirus of a lower vertebrate, and show that it is also related to dCK. Paper-6982414. The same differences concerning dCK and hENT1 mRNA expression were observed between MLL gene-rearranged (n = 14) and germ line MLL cases (n = 25). Paper-9659375. Docking simulation with a purine nucleoside specific homology model of deoxycytidine kinase, a target enzyme for anticancer and antiviral therapy. Paper-11298743. 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. Lymphoblast cell lines from subjects heterozygous for the coding changes had significantly lower DCK activity compared with homozygous WT subjects. Paper-12544285. Although compelling evidence indicated that dCK activity might be regulated by phosphorylation/dephosphorylation, direct demonstration was lacking. Paper-11317053. Whereas TK1 is only responsible for thymidine phosphorylation, dCK is capable of converting dC, dA, and dG into their monophosphate forms. Paper-13853077. The role of cytoplasmic deoxycytidine kinase in the mitochondrial effects of the anti-human immunodeficiency virus compound, 2',3'-dideoxycytidine. Paper-52401. The mammalian deoxyribonucleoside kinases are deoxycytidine kinase, thymidine kinase 1 and 2 and deoxyguanosine kinase. Paper-427232. Positive regulation of deoxycytidine kinase activity by phosphorylation of Ser-74 in B-cell chronic lymphocytic leukaemia lymphocytes. Paper-13283212. G-phase enriched tonsilar lymphocyte subpopulation treated by CdA showed more profound stimulation of dCK activity than S-phase cells. Paper-1483976. CONCLUSIONS: Variants in the A9846G SNP of the dCK gene were associated with sensitivity to gemcitabine in pancreatic cancer cell lines. Paper-15712742. Although araG is phosphorylated by dCK in vitro, it is a preferred substrate of mitochondrial deoxyguanosine kinase. Paper-8461203. With CdA as a substrate, the Michaelis constant (Km) of dCK in crude extracts of mouse thymus was 10 times higher than that in human thymus. Paper-381925. In addition, inactivation of dCK by point mutations, deletions or genomic rearrangements can easily be detected in AraC-resistant cell lines. Paper-8385325. Deoxycytidine kinase and cN-II nucleotidase expression in blast cells predict survival in acute myeloid leukaemia patients treated with cytarabine. Paper-9818039. 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. The present results suggest that dCK is also unable to discriminate the chirality of nucleotides at the phosphate donor binding site of the enzyme. Paper-1486188. In conclusion, we developed a new MSP method showing methylation of the 3' GC-box in the dCK promoter region in tumor cells and patient samples. Paper-15256856. 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 kinetic properties of mouse and human dCK differed in that the human enzyme showed higher affinity for the substrates dAdo, CdA, ddCyd and araG. Paper-305355. 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. 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. Structural basis for activation of the therapeutic L-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase. Paper-12424560. Cytotoxic activity of 2',2'-difluorodeoxycytidine, 5-aza-2'-deoxycytidine and cytosine arabinoside in cells transduced with deoxycytidine kinase gene. Paper-9482128. 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. Comparison of the substrate specificities of human thymidine kinase 1 and 2 and deoxycytidine kinase toward antiviral and cytostatic nucleoside analogs. Paper-6976012. 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. 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. In control samples from healthy donors (PHA T cells and bone marrow), only wild-type dCK complementary DNA (cDNA) was amplified. Paper-8378242. Structural and kinetic characterization of human deoxycytidine kinase variants able to phosphorylate 5-substituted deoxycytidine and thymidine analogues . Paper-15328630. The resistant phenotype in vitro is always a result of mutational inactivation of dCK, leading to defects in the metabolic pathways of AraC. Paper-8385325. 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. 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. Increased dCK/5'-NT activity was not correlated with increased efficacy ( cell death) or percentage of cellular [8-3H]-2-CdA converted to [8-3H]-2-CdATP ex vivo. Paper-10439890. 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. Gemcitabine resistance due to deoxycytidine kinase deficiency can be reverted by fruitfly deoxynucleoside kinase, DmdNK, in human uterine sarcoma cells. Paper-12055316. The results revealed a significant increase in dCK activity in bryostatin 1 treated cells at 48 and 72 h compared with the control. Paper-1675580. Sequencing revealed that exon 3 was deleted from the dCK cDNA, resulting in a 74-aa-long open-reading frame due to the generation of a premature stop codon. Paper-10509757. Activation of deoxycytidine kinase by deoxyadenosine: implications in deoxyadenosine-mediated cytotoxicity. Paper-11286292. 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. The complexes with UDP revealed an open state of dCK in which the nucleoside, either D-dA or L-dA, is surprisingly bound in a manner not consistent with catalysis. Paper-14311959. 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. The promoter and coding region of the DCK gene were analyzed in 74 follicular lymphoma (FL) patients receiving a therapeutic regimen that included fludarabine. Paper-15735119. Several series of mono- and di-substituted DCK derivatives (DCKs) have previously been synthesized, and their structure-activity relationships are well established. Paper-11535336. 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 role of HuR in gemcitabine efficacy in pancreatic cancer: HuR up-regulates the expression of the gemcitabine metabolizing enzyme deoxycytidine kinase. Paper-14049476. Cyclopentenyl cytosine-induced activation of deoxycytidine kinase increases gemcitabine anabolism and cytotoxicity in neuroblastoma. Paper-10564553. 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. Modifications of deoxycytidine kinase and deaminase activities by docosahexaenoic acid in normal and transformed rat fibroblasts. Paper-9450487. 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. Acquired resistance to CAFdA in HL60 and in CCRF-CEM cell lines was directly correlated to the decreased activity of the nucleoside phosphorylating enzyme, dCK. Paper-8292174. 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. A new pyrimidine-specific reporter gene: a mutated human deoxycytidine kinase suitable for PET during treatment with acycloguanosine-based cytotoxic drugs. Paper-15381446. 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. 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. Previous results demonstrated that dCTP was a potent competitive or noncompetitive (with respect to dCyd) inhibitor of dCK, with a Ki value of approximately 1 microM. Paper-7306471. 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. CONCLUSION: Down-regulation of dCK specifically enhanced acquired resistance to gemcitabine in pancreatic cancer cells without affecting their proliferation. Paper-12920813. 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. Staurosporine increased dCK activity about two-fold and the activity of thymidine kinase 2, which may also activate gemcitabine. Paper-15143307. 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. However, the only strong correlations with gemcitabine sensitivity are dCK activity and dFdCTP pools, with a potential important role for ribonucleotide reductase. Paper-9185908. We also demonstrate that ara-C treatment of established intradermal and intracerebral gliomas transduced with dCK results in significant antitumor effects in vivo. Paper-533828. 3-Deazauridine enhances the antileukemic action of 5-aza-2'-deoxycytidine and targets drug-resistance due to deficiency in deoxycytidine kinase. Paper-15586728. Deoxycytidine kinase (dCK) and deaminase (dCDA) are both key enzymes in the activation and inactivation, respectively, of several deoxycytidine antimetabolites. Paper-7763556. 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. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival. Paper-11824039. These observations aroused our interest in 3-deazauridine ( 3-DU), a CTP synthetase inhibitor that is effective against leukemic cells deficient in DCK. Paper-15586728. Furthermore, the dCTP concentration in intact cells, which is typically 10-20 microM, is not sufficient to cause substantial inhibition of dCK, due to the presence of UTP. Paper-7306471. AG6000 is cross-resistant to other drug which require activation by dCK, such as 1-beta-D-arabinofuranosylcytosine, 5-aza-2'-deoxycytidine, and 2-chlorodeoxyadenosine. Paper-8011166. 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. 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. These results indicate that CPEC enhances the cytotoxicity of dFdC alone and in combination with irradiation in several human tumour cell lines with an intact dCK gene. Paper-14302593. These data suggest that viral vector transduction of the dCK gene followed by treatment with ara-C represents a new chemosensitization strategy for cancer gene therapy. Paper-533828. In addition to accepting dC and purine nucleosides (and their analogs) as phosphoryl acceptors, dCK can utilize either ATP or UTP as phosphoryl donors. Paper-14311959. The differential states adopted by dCK in response to the nature of the nucleotide were also detected by tryptophan fluorescence experiments. Paper-14311959. In contrast, genistein, a general protein tyrosine kinase inhibitor, and AG-490, an inhibitor of JAK2 and JAK3, increased basal dCK activity more than two-fold. Paper-10299789. 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. Fluorescence energy transfer studies of human deoxycytidine kinase: role of cysteine 185 in the conformational changes that occur upon substrate binding. Paper-11802683. Methylation might therefore regulate transcription of dCK, and should be studied further to understand its role in influencing gemcitabine and cytarabine activity. Paper-15256856. Relationship between single nucleotide polymorphisms in the deoxycytidine kinase gene and chemosensitivity of gemcitabine in six pancreatic cancer cell lines. Paper-15712742. 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. 2-Chlorodeoxyadenosine (CdA) was used as the substrate for dCK and was separated from its product 2-chlorodeoxyadenosine-5'-monophosphate (CdAMP) by reversed-phase HPLC. Paper-10451374. Viral vector transduction of the human deoxycytidine kinase cDNA sensitizes glioma cells to the cytotoxic effects of cytosine arabinoside in vitro and in vivo. Paper-533828. As a result, the activity ratio of dCK/dCDA (a potential indicator of chemosensitivity) was decreased in the normal fibroblasts but increased in the transformed cells by DHA. Paper-9450487. 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. In this study, we show that cycloSaligenyl-2-chloro-2 '-deoxyadenosine monophosphate (cycloSal-CdAMP) is 10-fold more potent that CdA in a dCK-deficient lymphoma cell line. Paper-14731485. 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. On the other hand, the crude extract of these cells had about 10 times more deoxycytidine kinase than deoxythymidine kinase specific activity, as it was reported previously as well. Paper-5105336. To improve the low catalytic activity and tailor the substrate specificity of dCK, we have constructed libraries of mutant enzymes and tested them for thymidine kinase (tk) activity. Paper-14323871. In accord with the elevated enzyme activity, we observed a 6-fold increased dFdC incorporation into DNA and a more pronounced inhibition of DNA synthesis in the A-549- dCK cells. Paper-9482128. 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. These data suggest that the activation of dCK may be due to phosphorylation, and that deoxynucleoside salvage is promoted during inhibition of DNA synthesis in human lymphocytes. Paper-8685404. Detection of an alternatively spliced form of deoxycytidine kinase mRNA in the 2'-2'-difluorodeoxycytidine (gemcitabine)-resistant human ovarian cancer cell line AG6000. Paper-10509757. While 5-[3H]-thymidine (TdR) incorporation into DNA was decreased by 80-90%, dCK activity was doubled as a consequence of incubating the cells with 1 microM 2-chloro-2'-deoxyadenosine. Paper-1616837. In conclusion, staurosporine may potentiate gemcitabine by increasing dCK and decreasing E2F and RNR, which will lead to a more pronounced RNR inhibition. Paper-15143307. Activation of dCK by a number of genotoxic agents including 2-chlorodeoxyadenosine, a deamination-resistant deoxyadenosine analogue, was found previously. Paper-11286292. Our data showed that the human deoxycytidine kinase is located in the cell nucleus and the human deoxyguanosine kinase is located in the mitochondria. Paper-1225643. 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. 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. 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. 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. Deficiency of dCK is associated with resistance against this compound both in vitro in cancer cell lines and in clinical practice in acute myeloid leukemia and solid tumors. Paper-10509757. Therefore, the present study aimed to investigate the relationship between SNPs in the dCK gene and chemosensitivity to gemcitabine in human pancreatic cancer cell lines. Paper-15712742. CONCLUSION: The mutants of human dCK can be used as pyrimidine-specific PET reporter genes for imaging with (18)F-FEAU during treatment with acycloguanosine-based antiviral drugs. Paper-15381446. 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. 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. 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. Activation of dCK by UV-C was mimicked by H(2)O(2), markedly counteracted by N-acetylcysteine, a general antioxidant, and completely abolished by the growth factor receptor inhibitor suramin. Paper-9743106. 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. 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. Paper-6167882. 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. 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. Paper-6167882. 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. 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. Three major activities were resolved by ion exchange and affinity chromatography: deoxyguanosine- deoxycytidine kinase, deoxycytidine-deoxyadenosine kinase, and adenosine-deoxyadenosine kinase. Paper-4505526. CONCLUSIONS: dCK protein expression was identified as an independent and strong prognostic factor in patients with resected pancreatic adenocarcinoma who received adjuvant gemcitabine therapy. Paper-15496505. 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. However, detection of a single-stranded conformation polymorphism ( SSCP) allowed the identification of a single C to G substitution (His to Gln) in the dck cDNA of the DAC-resistant RD/1 clone. Paper-314148. This hypothesis is supported by the observation that mutations that enlarge the active site cavity in proximity to the nucleoside 5-position endow dCK with the ability to phosphorylate thymidine. Paper-15328630. In four cell lines ( A2780, OVCAR-3, WiDr and UM-SCC-14C), sources for some of the above mentioned tumours, a different pattern in dCK and dCDA was observed than in the corresponding tumours. Paper-7763556. 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. Staurosporine increases toxicity of gemcitabine in non-small cell lung cancer cells: role of protein kinase C, deoxycytidine kinase and ribonucleotide reductase. Paper-15143307. 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. We describe the ability of a tert-butyl S-acyl-thioethyl (SATE) derivative of ara-CMP (UA911) to circumvent ara-C resistance in a dCK-deficient human follicular lymphoma cell line (RL-G). Paper-10034354. 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. 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. We have previously reported the development of 1-(2'-deoxy-2'-(18)F-fluoro-beta-D-arabinofuranosyl)cytosine ((18)F-FAC), a new probe for PET of dCK activity in immune disorders and certain cancers. Paper-15276760. On multivariate analysis, dCK protein expression was the only independent prognostic variable (DFS: hazard ratio [HR], 3.48; 95% CI, 1.66-7.31; P = .001; OS: HR, 3.2; 95% CI,1.44-7.13; P = .004). Paper-15496505. 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. However, in conflict with this hypothesis was our discovery that the cytidine analogue 5-methyldeoxycytidine (5-Me-dC), an isostere of thymidine, can indeed be phosphorylated by wild-type (WT) dCK. Paper-15328630. 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. 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. 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. 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. Reverse-transcribed and PCR-amplified mRNA, using specific dCK primers, demonstrated that AG6000 expressed a normal length amplicon of 701 base pairs, besides an aberrant amplicon of 500 base pairs. Paper-8011166. Human B-lymphoblast cell extracts showed three peaks of nucleoside kinase activities, adenosine kinase (EC 2.7.1.20), deoxyguanosine kinase and deoxycytidine kinase (EC 2.7.1.74). Paper-4479518. While neither % S phase, DCK, nor overall Poly activity were predictive for early response, TK and Poly alpha activities were significantly higher for cases with adequate blast cell clearance. Paper-1154367. 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. Using an optimized dose-schedule we showed that this combination could cure some mice bearing L1210 leukemia, even in the presence of a subpopulation of drug-resistant (L1210/ARA-C) leukemic cells lacking DCK. Paper-15586728. 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. 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. In conclusion, the clear correlation between dCK levels and gemcitabine sensitivity in various murine tumors and human tumor xenografts may be a prognostic parameter when considering gemcitabine therapy. Paper-9653443. To evaluate the potential of dCK to be used as suicide gene for deoxycytidine nucleoside analogs, we transduced both human A-549 lung carcinoma and murine NIH3T3 fibroblast cell lines with this gene. Paper-9482128. The Km for CAFdA with dCK was also lower than that for CdA, as measured in crude extracts from the human acute lymphoblastic leukemia cell line CCRF-CEM and the promyelocytic leukemia cell line HL60. Paper-8292174. DHA supplementation increased the phosphorylation efficiency (V(max)/K(m)) of dCK but decreased the deamination efficacy of dCDA in the transformed cells as compared with those in the normal fibroblasts. Paper-9450487. 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. The present results demonstrate that both retroviral and adenoviral vector-mediated transduction of the dCK cDNA results in marked sensitization of glioma cells lines to the cytotoxic effects of ara-C in vitro. Paper-533828. Therefore, we propose that addition of ABCG2 inhibitors would effectively increase the antitumor efficacy of purine nucleosides by blocking drug efflux that may be a significant mode of resistance when dCK levels are low. Paper-15712480. TSK phosphorylated deoxycytidine, deoxyadenosine, deoxyguanosine and arabinocytidine, similar to dCK, but the respective kinetic properties were quite different. Paper-4940729. Because the level and function of dCK and ABCG2 vary substantially among other types of cancer, these findings have important implications not only for clofarabine therapy but for purine nucleoside therapy in general. Paper-15712480. 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. Recently, stimulation of dCK activity was shown by these analogues and by other genotoxic agents such as etoposide and NaF, all of which cause severe inhibition of DNA synthesis in cell cultures. Paper-8685404. 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. Using methylation specific PCR (MSP), methylation was detected in one of the SP1 binding sites of the dCK promoter, in most tested cancer cell lines and in patient samples from brain tumors and leukemia. Paper-15256856. 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. 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. Reverse transcribed and polymerase chain reaction amplified mRNA, using specific dCK primers, demonstrated that AG6000 expressed a normal length amplicon of 701 base pairs, besides an aberrant amplicon of 500 base pairs. Paper-386069. 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. 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. 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. 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. 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. These results demonstrate that continuous treatment of H9 cells in the presence of AZT selected for a thymidine analog resistant cell variant with cross-resistance to deoxycytidine analogs, due to deficiency in TK1, TK2, and dCK. Paper-9513359. We assume that dCK activation elicited by cellular damage might be a proapoptotic factor in terms of generating dATP well before the release of cytochrome c and deoxyguanosine kinase from mitochondria. Paper-10615271. 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. Potentiation of 2-chlorodeoxyadenosine activity by bryostatin 1 in the resistant chronic lymphocytic leukemia cell line (WSU-CLL): association with increased ratios of dCK/5'-NT and Bax/Bcl-2. Paper-1675580. 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. 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. 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. Here we describe that direct inhibition of DNA polymerases by aphidicolin stimulated dCK activity in normal lymphocytes and acute myeloid leukaemic cells, as well as in HL 60 promyelocytic cell cultures. Paper-8685404. 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. Fluorescence in situ hybridization on normal rat fibroblast metaphase spreads localized the rat dck gene to chromosome 14q21-q22, a region that was not involved in any of the observed karyotypic aberrations. Paper-314148. 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. 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. 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. 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. 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. 3H-Ara-C uptake was correlated with 3H-TdR incorporation ( r = 0.74) and with the (S-phase dependent) activities of TK ( r = 0.73) and poly alpha ( r = 0.71, but not with DCK activity or intracellular Ara-CTP content. Paper-411629. Human deoxycytidine kinase and thymidine kinase 1 are described as cytosolic enzymes in the literature, whereas human deoxyguanosine kinase and thymidine kinase 2 are believed to be located in the mitochondria. Paper-1225643. 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. 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. 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. 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. 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. This study demonstrates that dCK protein concentration levels were regulated by HuR and that a high cytoplasmic HuR level was associated with a sevenfold decreased risk of mortality after resection of pancreatic adenocarcinoma and gemcitabine therapy. Paper-14049476. 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. 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. 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. 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. 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. Paper-6167882. 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. 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 examined whether susceptibility of mouse colon carcinoma (Colon 26) and rat gliosarcoma (9L) cells to 1-beta-D-arabiofuranosylcytonsine (AraC), a chemotherapeutic agent, can be increased after the tumor cells were transduced with the human dCK gene. Paper-8378920. 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. 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. RESULTS: Cells transduced with dCK mutant reporter genes showed high in vitro and in vivo uptake of pyrimidine-based radiopharmaceuticals ((18)F-FEAU) comparable to that of herpes simplex virus type-1 thymidine kinase (HSV1-tk)-transduced cells. Paper-15381446. 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. 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 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. As protein kinase C (PKC) is higher in 2R120 and 2R160 cells and may control the dCK activity, we investigated whether gemcitabine sensitivity was affected by the protein kinase C inhibitor, staurosporine, which also modulates the cell cycle. Paper-15143307. 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. 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. 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. The bryostatin 1-induced increased ratio of dCK/5'-NT activity and an increased ratio of Bax/Bcl-2 are at least two mechanisms through which this natural compound is able to potentiate the anti-tumor activity of 2-CdA in otherwise resistant CLL cells. Paper-1675580. 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. An oligonucleotide microarray screen (Affymetrix) comparing patients with MLL gene-rearranged ALL with those with nonrearranged ALL also showed a 1.9-fold lower dCK ( P =.001) and a 2.7-fold higher hENT1 ( P =.046) mRNA expression in patients with MLL gene-rearranged ALL. Paper-9659375. Approximately 3 days after the end of the 5-Aza-C infusion, the HDara-C regimen was given again with the idea that the induced DNA hypomethylation in the leukemic cells may have increased the dCk activity and that a reversal of the tumor drug resistance to ara-C could have occurred. Paper-6494836. 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. 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. 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. 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. 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. The specific activities of nucleoside kinase enzymes in nanomoles per h per mg +/- SD were as follows: adenosine kinase, 30 +/- 14; deoxyadenosine kinase, 12 +/- 2; deoxycytidine kinase, 0.30 +/- 0.04; and deoxyguanosine kinase, 27 +/- 16. Paper-4505526. 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. 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. 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. To unravel the structural basis for substrate promiscuity of dCK at both the nucleoside acceptor and nucleotide donor sites, we solved the crystal structures of the enzyme as ternary complexes with the two enantiomeric forms of dA (D-dA, or L-dA), with either UDP or ADP bound to the donor site. Paper-14311959. Characterization of both clones revealed stably elevated levels of purine-specific "high-Michaelis constant (Km)" 5'-nucleotidase (5'-NT) messenger RNA expression and specific activity, whereas pyrimidine-specific "low-Km" 5'-NT activity was undetectable, and dCK activity was only marginally decreased in R13. Paper-1660694. 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. CCRF/ CEM/0 (wild type), CCRF/ CEM/ara-C/7A (approximately 50% ara-C-resistant as determined by ara-C sensitivity assay and dCk characterization), and CCRF/ CEM/ara-C/3A (approximately 90% resistant to ara-C) human leukemia cells were incubated with various concentrations of 6-MP and ara-C given alone or in combination. Paper-147555. Its apparent molecular weight was estimated to be 49,000 and its Stokes radius 30 A. Two other minor peaks of deoxyadenosine-phosphorylating activity had characteristics different from either deoxycytidine kinase or adenosine kinase-associated deoxyadenosine kinase. Paper-4505526. 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. 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. Because secondary modifications of enzymes usually involve the signalling processes in cells, the universal G-protein activator fluorine ions were tested. dCK activity of human lymph node lymphocytes were increased 2-times, if cells were incubated in the presence of NaF for 1-2 hrs in cultures, while TK activity was not changed. Paper-1483935. 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. METHODS: We have developed and characterized a gemcitabine-resistant cell line (Messa 10 K) from the human uterine sarcoma Messa strain, and transfected this cell line with the multisubstrate deoxynucleoside kinase from Drosophila melanogaster (DmdNK) in order to revert the resistance in Messa 10 K cells which was due to dCK-deficiency. Paper-12055316. 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. 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), CR541876 (NCBI_GENBANK__AC), CR536527 (NCBI_GENBANK__AC). DCK is a homologue of Os05g0430200 (Os05g0430200) from Oryza sativa Japonica Group. DCK is a homologue of DCK (deoxycytidine kinase) from Pan troglodytes. DCK is a homologue of DCK (deoxycytidine kinase) from Canis lupus familiaris. DCK is a homologue of DCK (deoxycytidine kinase) from Bos taurus. DCK is a homologue of DCK (deoxycytidine kinase) from Gallus gallus. 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.