deoxycytidine kinase

Summary

Summary: An enzyme that catalyzes reversibly the phosphorylation of deoxycytidine with the formation of a nucleoside diphosphate and deoxycytidine monophosphate. Cytosine arabinoside can also act as an acceptor. All natural nucleoside triphosphates, except deoxycytidine triphosphate, can act as donors. The enzyme is induced by some viruses, particularly the herpes simplex virus (HERPESVIRUS HOMINIS). EC 2.7.1.74.

Top Publications

  1. Parker W, Shaddix S, Rose L, Shewach D, Hertel L, Secrist J, et al. Comparison of the mechanism of cytotoxicity of 2-chloro-9-(2-deoxy-2- fluoro-beta-D-arabinofuranosyl)adenine, 2-chloro-9-(2-deoxy-2-fluoro- beta-D-ribofuranosyl)adenine, and 2-chloro-9-(2-deoxy-2,2-difluoro- beta-D-ribofuranosyl)adenine in CEM cells. Mol Pharmacol. 1999;55:515-20 pubmed
    ..The compounds were similar as substrates of deoxycytidine kinase. Similar amounts of their respective triphosphates accumulated in CEM cells, and the rate of disappearance ..
  2. Song J, Kim S, Kweon S, Lee T, Kim H, Kim H, et al. Defective expression of deoxycytidine kinase in cytarabine-resistant acute myeloid leukemia cells. Int J Oncol. 2009;34:1165-71 pubmed
    ..The results of the microarray analysis revealed a severe defect in the expression of deoxycytidine kinase (dCK), which plays a key role in the transformation of Ara-C to the active form in AML-2/IDAC cells...
  3. Ohhashi S, Ohuchida K, Mizumoto K, Fujita H, Egami T, Yu J, et al. Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer. Anticancer Res. 2008;28:2205-12 pubmed
    The functional roles of deoxycytidine kinase (dCK) in acquired resistance to gemcitabine remain unknown in pancreatic cancer. Here, the functional involvement of dCK in gemcitabine-resistance of pancreatic cancer was investigated...
  4. Sabini E, Hazra S, Konrad M, Lavie A. Nonenantioselectivity property of human deoxycytidine kinase explained by structures of the enzyme in complex with L- and D-nucleosides. J Med Chem. 2007;50:3004-14 pubmed
    ..The first step in the activation of these agents is catalyzed by human deoxycytidine kinase (dCK). This enzyme possesses the ability to phosphorylate nucleosides of the unnatural L-chirality...
  5. Van Den Neste E, Smal C, Cardoen S, Delacauw A, Frankard J, Ferrant A, et al. Activation of deoxycytidine kinase by UV-C-irradiation in chronic lymphocytic leukemia B-lymphocytes. Biochem Pharmacol. 2003;65:573-80 pubmed
    b>Deoxycytidine kinase (dCK), a key enzyme of the deoxynucleoside salvage pathway, might have a preponderant role in DNA synthesis in resting chronic lymphocytic leukemia B-lymphocytes...
  6. Sabini E, Hazra S, Konrad M, Burley S, Lavie A. Structural basis for activation of the therapeutic L-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase. Nucleic Acids Res. 2007;35:186-92 pubmed
    ..Herein, we report the crystal structures of human deoxycytidine kinase (dCK) in complex with the L-nucleosides (-)-beta-2',3'-dideoxy-3'-thiacytidine (3TC)--an approved anti-..
  7. Murphy J, Armijo A, Nomme J, Lee C, Smith Q, Li Z, et al. Development of new deoxycytidine kinase inhibitors and noninvasive in vivo evaluation using positron emission tomography. J Med Chem. 2013;56:6696-708 pubmed publisher
    Combined inhibition of ribonucleotide reductase and deoxycytidine kinase (dCK) in multiple cancer cell lines depletes deoxycytidine triphosphate pools leading to DNA replication stress, cell cycle arrest, and apoptosis...
  8. Weng T, Karmouty Quintana H, Garcia Morales L, Molina J, Pedroza M, Bunge R, et al. Hypoxia-induced deoxycytidine kinase expression contributes to apoptosis in chronic lung disease. FASEB J. 2013;27:2013-26 pubmed publisher
    ..Our results suggest that activating the dAdo-DCK-dATP pathway directly results in increased apoptosis in the lungs of mice with air-space enlargement and suggests a novel therapeutic target for the treatment of COPD. ..
  9. Geutjes E, Tian S, Roepman P, Bernards R. Deoxycytidine kinase is overexpressed in poor outcome breast cancer and determines responsiveness to nucleoside analogs. Breast Cancer Res Treat. 2012;131:809-18 pubmed publisher
    ..to the clinically important nucleoside analogs gemcitabine and decitabine may be critically determined by Deoxycytidine kinase (DCK) expression as this enzyme is required to convert the inactive prodrugs into their pharmacologically ..

More Information

Publications62

  1. Hazra S, Szewczak A, Ort S, Konrad M, Lavie A. Post-translational phosphorylation of serine 74 of human deoxycytidine kinase favors the enzyme adopting the open conformation making it competent for nucleoside binding and release. Biochemistry. 2011;50:2870-80 pubmed publisher
    b>Deoxycytidine kinase (dCK) uses either ATP or UTP as a phosphoryl donor to catalyze the phosphorylation of nucleoside acceptors. The kinetic properties of human dCK are modulated in vivo by phosphorylation of serine 74...
  2. Fujita H, Ohuchida K, Mizumoto K, Itaba S, Ito T, Nakata K, et al. Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy. Neoplasia. 2010;12:807-17 pubmed
  3. Costantino C, Witkiewicz A, Kuwano Y, Cozzitorto J, Kennedy E, Dasgupta A, et al. The role of HuR in gemcitabine efficacy in pancreatic cancer: HuR Up-regulates the expression of the gemcitabine metabolizing enzyme deoxycytidine kinase. Cancer Res. 2009;69:4567-72 pubmed publisher
    ..In pancreatic cancer cells, HuR associates with deoxycytidine kinase (dCK) mRNA, which encodes the enzyme that metabolizes and thereby activates gemcitabine...
  4. Kim S, Saito Y, Maekawa K, Sugiyama E, Kaniwa N, Ueno H, et al. Twenty novel genetic variations and haplotype structures of the DCK gene encoding human deoxycytidine kinase (dCK). Drug Metab Pharmacokinet. 2008;23:379-84 pubmed
    b>Deoxycytidine kinase (dCK) is a rate-limiting enzyme in the activation of nucleoside anticancer drugs, such as gemcitabine and cytarabine (Ara-C), to their active metabolites...
  5. Szatmári T, Huszty G, Desaknai S, Spasokoukotskaja T, Sasvari Szekely M, Staub M, et al. Adenoviral vector transduction of the human deoxycytidine kinase gene enhances the cytotoxic and radiosensitizing effect of gemcitabine on experimental gliomas. Cancer Gene Ther. 2008;15:154-64 pubmed publisher
    ..Gl261, rat C6 and human U373 glioma cell lines were transduced with an adenoviral vector encoding the human deoxycytidine kinase gene (Ad-HudCK)...
  6. Jordheim L, Galmarini C, Dumontet C. Gemcitabine resistance due to deoxycytidine kinase deficiency can be reverted by fruitfly deoxynucleoside kinase, DmdNK, in human uterine sarcoma cells. Cancer Chemother Pharmacol. 2006;58:547-54 pubmed
    ..Resistance to these compounds is frequent and often multifactorial. Deficiency in deoxycytidine kinase (dCK), the rate-limiting activating enzyme, has been reported in a number of in vitro models as well as in ..
  7. Hatzis P, Al Madhoon A, Jullig M, Petrakis T, Eriksson S, Talianidis I. The intracellular localization of deoxycytidine kinase. J Biol Chem. 1998;273:30239-43 pubmed
    b>Deoxycytidine kinase (dCK) catalyzes the rate-limiting step of the deoxynucleoside salvage pathway in mammalian cells and plays a key role in the activation of several pharmacologically important nucleoside analogs...
  8. Kawasaki H, Shindou K, Higashigawa M, Cao D, Hori H, Ido M, et al. Deoxycytidine kinase mRNA levels in leukemia cells with competitive polymerase chain reaction assay. Leuk Res. 1996;20:677-82 pubmed
    b>Deoxycytidine kinase (dCyd kinase) is important for the phosphorylation of several different nucleoside antimetabolites...
  9. Kwon W, Rha S, Choi Y, Lee J, Park K, Jung J, et al. Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines. Pharmacogenet Genomics. 2006;16:429-38 pubmed
    ..Polymorphisms of gemcitabine metabolism-related genes of deoxycytidine monophosphate deaminase (DCTD), deoxycytidine kinase (DCK) and ribonucleotide reductase M1 (RRM1) were evaluated using the CEQ8000 Genetic analysis system and ..
  10. Lotfi K, Mansson E, Chandra J, Wang Y, Xu D, Knaust E, et al. Pharmacological basis for cladribine resistance in a human acute T lymphoblastic leukaemia cell line selected for resistance to etoposide. Br J Haematol. 2001;113:339-46 pubmed
    ..The activity of deoxycytidine kinase (dCK), responsible for activation of CdA and ara-C, was the same for resistant and wild-type cells...
  11. Iyidogan P, Lutz S. Systematic exploration of active site mutations on human deoxycytidine kinase substrate specificity. Biochemistry. 2008;47:4711-20 pubmed publisher
    Human deoxycytidine kinase (dCK) is responsible for the phosphorylation of a number of clinically important nucleoside analogue prodrugs in addition to its natural substrates, 2'-deoxycytidine, 2'-deoxyguanosine, and 2'-deoxyadenosine...
  12. Lamba J, Crews K, Pounds S, Schuetz E, Gresham J, Gandhi V, et al. Pharmacogenetics of deoxycytidine kinase: identification and characterization of novel genetic variants. J Pharmacol Exp Ther. 2007;323:935-45 pubmed
    b>Deoxycytidine kinase (DCK) is a rate-limiting enzyme in the activation of nucleoside analogs such as cytarabine (ara-C), gemcitabine, clofarabine, and others...
  13. Schirmer M, Stegmann A, Geisen F, Konwalinka G. Lack of cross-resistance with gemcitabine and cytarabine in cladribine-resistant HL60 cells with elevated 5'-nucleotidase activity. Exp Hematol. 1998;26:1223-8 pubmed
    ..gemcitabine) and 1-beta-D-arabinofuranosylcytosine (cytosine arabinoside, cytarabine) with reduced deoxycytidine kinase (dCK) activity as the underlying determinant of resistance...
  14. Joerger M, Bosch T, Doodeman V, Beijnen J, Smits P, Schellens J. Novel deoxycytidine kinase gene polymorphisms: a population screening study in Caucasian healthy volunteers. Eur J Clin Pharmacol. 2006;62:681-4 pubmed
    b>Deoxycytidine kinase (DCK) is the rate-limiting enzyme of the intracellular phosphorylation of nucleoside anticancer drugs, including gemcitabine and beta-arabinofuranosylcytosine, to their active triphosphates...
  15. Stam R, den Boer M, Meijerink J, Ebus M, Peters G, Noordhuis P, et al. Differential mRNA expression of Ara-C-metabolizing enzymes explains Ara-C sensitivity in MLL gene-rearranged infant acute lymphoblastic leukemia. Blood. 2003;101:1270-6 pubmed
    ..reaction (RT-PCR) (TaqMan) revealed that infants express 2-fold less of the Ara-C phosphorylating enzyme deoxycytidine kinase (dCK) mRNA (P =.026) but 2...
  16. Giovannetti E, Mey V, Danesi R, Mosca I, Del Tacca M. Synergistic cytotoxicity and pharmacogenetics of gemcitabine and pemetrexed combination in pancreatic cancer cell lines. Clin Cancer Res. 2004;10:2936-43 pubmed
    ..Cytotoxicity of gemcitabine was examined with inhibitors of (a) deoxycytidine kinase (dCK), which activates gemcitabine by phosphorylation, and (b) 5'-nucleotidase (drug dephosphorylation) and ..
  17. Yang C, Lee M, Hao J, Cui X, Guo X, Smal C, et al. Deoxycytidine kinase regulates the G2/M checkpoint through interaction with cyclin-dependent kinase 1 in response to DNA damage. Nucleic Acids Res. 2012;40:9621-32 pubmed publisher
    b>Deoxycytidine kinase (dCK) is a rate limiting enzyme critical for phosphorylation of endogenous deoxynucleosides for DNA synthesis and exogenous nucleoside analogues for anticancer and antiviral drug actions...
  18. Raynal N, Momparler L, Rivard G, Momparler R. 3-Deazauridine enhances the antileukemic action of 5-aza-2'-deoxycytidine and targets drug-resistance due to deficiency in deoxycytidine kinase. Leuk Res. 2011;35:110-8 pubmed publisher
    ..5-AZA-CdR is a prodrug that is activated by deoxycytidine kinase (DCK). Leukemic cells lacking DCK are drug-resistant...
  19. Bouffard D, Laliberte J, Momparler R. Kinetic studies on 2',2'-difluorodeoxycytidine (Gemcitabine) with purified human deoxycytidine kinase and cytidine deaminase. Biochem Pharmacol. 1993;45:1857-61 pubmed
    Phosphorylation of cytosine analogs by deoxycytidine kinase (dCK) and deamination by cytidine deaminase (CDA) are two important processes in the activation and elimination of these drugs...
  20. Austin W, Armijo A, Campbell D, Singh A, Hsieh T, Nathanson D, et al. Nucleoside salvage pathway kinases regulate hematopoiesis by linking nucleotide metabolism with replication stress. J Exp Med. 2012;209:2215-28 pubmed publisher
    ..a functional link between nucleotide deficiency, RS, and the nucleoside salvage pathway (NSP) enzymes deoxycytidine kinase (dCK) and thymidine kinase (TK1)...
  21. Choi O, Heathcote D, Ho K, Müller P, Ghani H, Lam E, et al. A deficiency in nucleoside salvage impairs murine lymphocyte development, homeostasis, and survival. J Immunol. 2012;188:3920-7 pubmed publisher
    ..In this article, we describe a deficiency in deoxycytidine kinase (DCK), one of the major enzymes of the nucleoside salvage pathway, which affects peripheral T cell ..
  22. Zhang Y, Secrist J, Ealick S. The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation. Acta Crystallogr D Biol Crystallogr. 2006;62:133-9 pubmed
    ..Clofarabine is phosphorylated intracellularly by human deoxycytidine kinase (dCK) to the 5'-monophosphate, which is the rate-limiting step in activation of the prodrug...
  23. Keszler G, Spasokoukotskaja T, Csapo Z, Virga S, Staub M, Sasvari Szekely M. Selective increase of dATP pools upon activation of deoxycytidine kinase in lymphocytes: implications in apoptosis. Nucleosides Nucleotides Nucleic Acids. 2004;23:1335-42 pubmed
    Stimulation of the activity of deoxycytidine kinase (dCK), the principal deoxynucleoside salvage enzyme, has been recently considered as a protective cellular response to a wide range of agents interfering with DNA repair and apoptosis...
  24. Sigmond J, Kroep J, Loves W, Codacci Pisanelli G, Peters G. Quantitative real time PCR of deoxycytidine kinase mRNA by Light Cycler PCR in relation to enzyme activity and gemcitabine sensitivity. Cancer Lett. 2004;213:173-9 pubmed
    b>Deoxycytidine kinase (dCK) is essential for the phosphorylation of gemcitabine and can predict response to gemcitabine in vivo...
  25. Ohmine K, Kawaguchi K, Ohtsuki S, Motoi F, Egawa S, Unno M, et al. Attenuation of phosphorylation by deoxycytidine kinase is key to acquired gemcitabine resistance in a pancreatic cancer cell line: targeted proteomic and metabolomic analyses in PK9 cells. Pharm Res. 2012;29:2006-16 pubmed publisher
    ..The protein concentration of deoxycytidine kinase (dCK) in RPK9 cells was less than 0...
  26. Ge Y, Jensen T, Matherly L, Taub J. Physical and functional interactions between USF and Sp1 proteins regulate human deoxycytidine kinase promoter activity. J Biol Chem. 2003;278:49901-10 pubmed
    b>Deoxycytidine kinase (EC 2.7.1.74, dCK) is central to drug activity of anticancer and antiviral agents such as cytosine arabinoside (araC) and gemcitabine...
  27. Yu X, Miranda M, Liu Z, Patel S, Nguyen N, Carson K, et al. Novel potent inhibitors of deoxycytidine kinase identified and compared by multiple assays. J Biomol Screen. 2010;15:72-9 pubmed publisher
    b>Deoxycytidine kinase (dCK) phosphorylates deoxycytidine, deoxyguanosine, and deoxyadenosine and plays an important role in the salvage pathway of nucleoside metabolism...
  28. Sabini E, Hazra S, Ort S, Konrad M, Lavie A. Structural basis for substrate promiscuity of dCK. J Mol Biol. 2008;378:607-21 pubmed publisher
    b>Deoxycytidine kinase (dCK) is an essential nucleoside kinase critical for the production of nucleotide precursors for DNA synthesis...
  29. Kroep J, Loves W, van der Wilt C, Alvarez E, Talianidis I, Boven E, et al. Pretreatment deoxycytidine kinase levels predict in vivo gemcitabine sensitivity. Mol Cancer Ther. 2002;1:371-6 pubmed
    b>Deoxycytidine kinase (dCK) is essential for the phosphorylation of gemcitabine (2',2'-difluorodeoxycytidine), a deoxycytidine analogue active against various solid tumors. Cytidine deaminase (CDA) catalyzes the degradation of gemcitabine...
  30. Stegmann A, Honders M, Kester M, Landegent J, Willemze R. Role of deoxycytidine kinase in an in vitro model for AraC- and DAC-resistance: substrate-enzyme interactions with deoxycytidine, 1-beta-D-arabinofuranosylcytosine and 5-aza-2'-deoxycytidine. Leukemia. 1993;7:1005-11 pubmed
    b>Deoxycytidine kinase activity (dCk) was monitored in cell lines from a rat acute myeloid leukemia model of acquired resistance to cytosine arabinoside (AraC) and decitabine (DAC)...
  31. Nagai S, Takenaka K, Nachagari D, Rose C, Domoney K, Sun D, et al. Deoxycytidine kinase modulates the impact of the ABC transporter ABCG2 on clofarabine cytotoxicity. Cancer Res. 2011;71:1781-91 pubmed publisher
    ..However, their effectiveness depends on an initial activation step in which they are monophosphorylated by deoxycytidine kinase (dCK)...
  32. Achiwa H, Oguri T, Sato S, Maeda H, Niimi T, Ueda R. Determinants of sensitivity and resistance to gemcitabine: the roles of human equilibrative nucleoside transporter 1 and deoxycytidine kinase in non-small cell lung cancer. Cancer Sci. 2004;95:753-7 pubmed
    ..RT-PCR to examine the expression levels of human equilibrative nucleoside transporter 1 (hENT1) and deoxycytidine kinase (dCK) genes in non-small cell lung cancer (NSCLC) cell lines in relation to sensitivity and resistance to ..
  33. Pauwels B, Korst A, Pattyn G, Lambrechts H, Kamphuis J, de Pooter C, et al. The relation between deoxycytidine kinase activity and the radiosensitising effect of gemcitabine in eight different human tumour cell lines. BMC Cancer. 2006;6:142 pubmed
    ..In the present study, the relation between deoxycytidine kinase (dCK) activity and the radiosensitising effect of gemcitabine was investigated in eight different human ..
  34. Groschel B, Kaufmann A, Höver G, Cinatl J, Doerr H, Noordhuis P, et al. 3'-Azido-2',3'-dideoxythymidine induced deficiency of thymidine kinases 1, 2 and deoxycytidine kinase in H9 T-lymphoid cells. Biochem Pharmacol. 2002;64:239-46 pubmed
    ..analogs in AZT-resistant H9 cells revealed decreased mRNA levels of thymidine kinase 1 (TK1) and lack of deoxycytidine kinase (dCK) mRNA expression...
  35. Smal C, Ntamashimikiro S, Arts A, Van den Neste E, Bontemps F. Influence of phosphorylation of THR-3, SER-11, and SER-15 on deoxycytidine kinase activity and stability. Nucleosides Nucleotides Nucleic Acids. 2010;29:404-7 pubmed publisher
    b>Deoxycytidine kinase (dCK) is a key enzyme in the salvage of deoxyribonucleosides and in the activation of several anticancer and antiviral nucleoside analogues. We have recently shown that dCK is a phosphoprotein...
  36. Metharom E, Galettis P, Manners S, Links M. Modulation of gemcitabine accumulation by DNA-damaging agents: mechanisms and specificity in an in vitro model. Anticancer Res. 2010;30:3669-73 pubmed
    ..In this model, induction of gemcitabine accumulation is likely to be mediated by post translational modification of dCK. The reduced effect of oxaliplatin compared to cisplatin is worthy of further study. ..
  37. Sigmond J, Haveman J, Kreder N, Loves W, van Bree C, Franken N, et al. Enhanced activity of deoxycytidine kinase after pulsed low dose rate and single dose gamma irradiation. Nucleosides Nucleotides Nucleic Acids. 2006;25:1177-80 pubmed
    ..In this study, the effect of irradiation on the deoxycytidine kinase (dCK) needed for DNA repair was investigated...
  38. Hazra S, Sabini E, Ort S, Konrad M, Lavie A. Extending thymidine kinase activity to the catalytic repertoire of human deoxycytidine kinase. Biochemistry. 2009;48:1256-63 pubmed publisher
    Salvage of nucleosides in the cytosol of human cells is carried out by deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1)...
  39. Keszler G, Virga S, Spasokoukotskaja T, Bauer P, Sasvari Szekely M, Staub M. Activation of deoxycytidine kinase by deoxyadenosine: implications in deoxyadenosine-mediated cytotoxicity. Arch Biochem Biophys. 2005;436:69-77 pubmed
    ..Formation of dATP requires phosphorylation of deoxyadenosine by deoxycytidine kinase (dCK), the main nucleoside salvage enzyme in lymphoid cells...
  40. Gregoire V, Rosier J, De Bast M, Bruniaux M, De Coster B, Octave Prignot M, et al. Role of deoxycytidine kinase (dCK) activity in gemcitabine's radioenhancement in mice and human cell lines in vitro. Radiother Oncol. 2002;63:329-38 pubmed
    ..b>Deoxycytidine kinase (dCK) is the enzyme involved in the first phosphorylation cascade, and several observations have suggested ..
  41. Shu C, Campbell D, Lee J, Tran A, Wengrod J, Witte O, et al. Novel PET probes specific for deoxycytidine kinase. J Nucl Med. 2010;51:1092-8 pubmed publisher
    b>Deoxycytidine kinase (dCK) is a rate-limiting enzyme in the deoxyribonucleoside salvage pathway and a critical determinant of therapeutic activity for several nucleoside analog prodrugs...
  42. Veuger M, Honders M, Willemze R, Barge R. Deoxycytidine kinase expression and activity in patients with resistant versus sensitive acute myeloid leukemia. Eur J Haematol. 2002;69:171-8 pubmed
    ..In contrast to in vitro AraC resistance, deoxycytidine kinase (dCK) mutations are rarely found in patients with refractory or relapsed AML...
  43. Chottiner E, Shewach D, Datta N, Ashcraft E, Gribbin D, Ginsburg D, et al. Cloning and expression of human deoxycytidine kinase cDNA. Proc Natl Acad Sci U S A. 1991;88:1531-5 pubmed
    ..These findings document that this cDNA encodes the T-lymphoblast dCyd kinase responsible for the phosphorylation of dAdo and dGuo as well as dCyd and arabinofuranosylcytosine. ..
  44. Rodriguez C, Mitchell B, Ayres M, Eriksson S, Gandhi V. Arabinosylguanine is phosphorylated by both cytoplasmic deoxycytidine kinase and mitochondrial deoxyguanosine kinase. Cancer Res. 2002;62:3100-5 pubmed
    ..Although in vitro investigations using purified deoxycytidine kinase (dCK) or deoxyguanosine kinase (dGK) suggested that ara-G is a substrate for both enzymes, controversy ..
  45. Davidson J, Ma L, Flagella M, Geeganage S, Gelbert L, Slapak C. An increase in the expression of ribonucleotide reductase large subunit 1 is associated with gemcitabine resistance in non-small cell lung cancer cell lines. Cancer Res. 2004;64:3761-6 pubmed
    ..The results from this study indicate that the level of RRM1 may affect gemcitabine response. Furthermore, RRM1 may serve as a biomarker for gemcitabine response. ..
  46. Laugel B, Borlat F, Galibert L, Vicari A, Weissert R, Chvatchko Y, et al. Cladribine inhibits cytokine secretion by T cells independently of deoxycytidine kinase activity. J Neuroimmunol. 2011;240-241:52-7 pubmed publisher
    ..Here we demonstrate that clinically relevant concentrations of cladribine also inhibit cytokine secretion by human peripheral blood T cells in vitro through mechanisms independent of the induction of lymphocyte death. ..
  47. van Bree C, Castro Kreder N, Loves W, Franken N, Peters G, Haveman J. Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines. Int J Radiat Oncol Biol Phys. 2002;54:237-44 pubmed
    ..Bivariate flowcytometry was performed to study cell cycle changes. In the SWg, a complete deoxycytidine kinase (dCK) deficiency was found on mRNA and protein level...
  48. McSorley T, Ort S, Hazra S, Lavie A, Konrad M. Mimicking phosphorylation of Ser-74 on human deoxycytidine kinase selectively increases catalytic activity for dC and dC analogues. FEBS Lett. 2008;582:720-4 pubmed publisher
    ..We note that phosphorylation may represent a mechanism to enhance the catalytic activity of the relatively slow dCK enzyme. ..
  49. Dumontet C, Fabianowska Majewska K, Mantincic D, Callet Bauchu E, Tigaud I, Gandhi V, et al. Common resistance mechanisms to deoxynucleoside analogues in variants of the human erythroleukaemic line K562. Br J Haematol. 1999;106:78-85 pubmed
    ..5' nucleotidase activity was strongly increased and deoxycytidine kinase activity was moderately reduced in all of the resistant variants, resulting in reduced accumulation of ..
  50. Kocabas N, Aksoy P, Pelleymounter L, Moon I, Ryu J, Gilbert J, et al. Gemcitabine pharmacogenomics: deoxycytidine kinase and cytidylate kinase gene resequencing and functional genomics. Drug Metab Dispos. 2008;36:1951-9 pubmed publisher
    Gemcitabine and other cytidine antimetabolites require metabolic activation by phosphorylation. Deoxycytidine kinase (DCK) and cytidine monophosphate kinase (CMPK) catalyze these reactions...
  51. Smal C, Van Den Neste E, Maerevoet M, Poiré X, Theate I, Bontemps F. Positive regulation of deoxycytidine kinase activity by phosphorylation of Ser-74 in B-cell chronic lymphocytic leukaemia lymphocytes. Cancer Lett. 2007;253:68-73 pubmed
    b>Deoxycytidine kinase (dCK) activates several antileukaemic nucleoside analogues. We have recently reported that the activity of dCK, overexpressed in HEK 293T cells, correlates with its phosphorylation level on Ser-74...
  52. Sugiyama E, Kaniwa N, Kim S, Hasegawa R, Saito Y, Ueno H, et al. Population pharmacokinetics of gemcitabine and its metabolite in Japanese cancer patients: impact of genetic polymorphisms. Clin Pharmacokinet. 2010;49:549-58 pubmed publisher
    ..transported into cells by equilibrative and concentrative nucleoside transporters, it is phosphorylated by deoxycytidine kinase (DCK) and further phosphorylated to its active diphosphorylated and triphosphorylated forms...
  53. Mansson E, Flordal E, Liliemark J, Spasokoukotskaja T, Elford H, Lagercrantz S, et al. Down-regulation of deoxycytidine kinase in human leukemic cell lines resistant to cladribine and clofarabine and increased ribonucleotide reductase activity contributes to fludarabine resistance. Biochem Pharmacol. 2003;65:237-47 pubmed
    ..These analogues are pro-drugs and must be activated by deoxycytidine kinase (dCK)...