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Gene Review

DCK  -  deoxycytidine kinase

Homo sapiens

Synonyms: Deoxycytidine kinase, dCK
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Disease relevance of DCK


High impact information on DCK


Chemical compound and disease context of DCK


Biological context of DCK


Anatomical context of DCK

  • Northern blot analysis determined the length of dGK mRNA to 1.3 kbp with no cross-hybridization to the 2.8-kbp dCK mRNA. dGK mRNA was detected in all tissues investigated with the highest expression levels in muscle, brain, liver, and lymphoid tissues [14].
  • When ara-G was used as a substrate in a cell-free system, the maximum accumulation of phosphorylated product was observed in dGK+ extracts at low ara-G levels (10 microM) and in dCK+ extracts at high concentrations of ara-G (100 microM) [15].
  • For this purpose, dCK and dGK analyses were done in blood cells from 59 untreated symptomatic patients with CLL [17].
  • 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 [5].
  • High levels of dCK were found in normal mononuclear leukocytes (91-145 ng dCK/mg protein) and in B-cell chronic lymphocytic leukemia (80 +/- 30 ng/mg, n = 23) [5].

Associations of DCK with chemical compounds


Enzymatic interactions of DCK

  • Direct enzymatic phosphorylation does not seem to be essential to the mechanism of action of the nucleoside insofar as competitive inhibition of deoxycytidine kinase (an enzyme that directly phosphorylates purines as well as pyrimidines) or of deoxyguanosine kinase fails to inhibit 8BrGuo stimulation selectively [18].
  • 5'-Nucleotidase (5'-NT) dephosphorylates cladribine-MP and the accumulation of cladribine-TP depends on the ratio of dCK and 5'-NT in the cells [19].

Other interactions of DCK

  • The decline to normal levels of dCK concurred with a further increase in the activity of TK1, 8 h after irradiation [9].
  • From the available dCK, dGK and 5'-NT cDNA sequences we designed specific primers and fluorogenic probes for the respective genes [16].
  • Role of USF1 in the differential expression of the human deoxycytidine kinase gene in acute myeloid leukemia [20].
  • Several 5'-substituted analogues of dC were good non-substrate inhibitors of dCK and, to a lesser extent, of TK2 [21].
  • 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 [22].

Analytical, diagnostic and therapeutic context of DCK


  1. Characterization of the deoxycytidine kinase promoter in human lymphoblast cell lines. Chen, E.H., Johnson, E.E., Vetter, S.M., Mitchell, B.S. J. Clin. Invest. (1995) [Pubmed]
  2. Physical and functional interactions between USF and Sp1 proteins regulate human deoxycytidine kinase promoter activity. Ge, Y., Jensen, T.L., Matherly, L.H., Taub, J.W. J. Biol. Chem. (2003) [Pubmed]
  3. Deoxycytidine kinase and deoxyguanosine kinase of Lactobacillus acidophilus R-26 are colinear products of a single gene. Ma, N., Ikeda, S., Guo, S., Fieno, A., Park, I., Grimme, S., Ikeda, T., Ives, D.H. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  4. Cross-resistance in the 2',2'-difluorodeoxycytidine (gemcitabine)-resistant human ovarian cancer cell line AG6000 to standard and investigational drugs. Bergman, A.M., Giaccone, G., van Moorsel, C.J., Mauritz, R., Noordhuis, P., Pinedo, H.M., Peters, G.J. Eur. J. Cancer (2000) [Pubmed]
  5. Properties and levels of deoxynucleoside kinases in normal and tumor cells; implications for chemotherapy. Eriksson, S., Arnér, E., Spasokoukotskaja, T., Wang, L., Karlsson, A., Brosjö, O., Gunvén, P., Julusson, G., Liliemark, J. Adv. Enzyme Regul. (1994) [Pubmed]
  6. Differential phosphorylation of azidothymidine, dideoxycytidine, and dideoxyinosine in resting and activated peripheral blood mononuclear cells. Gao, W.Y., Shirasaka, T., Johns, D.G., Broder, S., Mitsuya, H. J. Clin. Invest. (1993) [Pubmed]
  7. Cytosine arabinoside transport and metabolism in acute leukemias and T cell lymphoblastic lymphoma. Wiley, J.S., Taupin, J., Jamieson, G.P., Snook, M., Sawyer, W.H., Finch, L.R. J. Clin. Invest. (1985) [Pubmed]
  8. Effect of uracil arabinoside on metabolism and cytotoxicity of cytosine arabinoside in L5178Y murine leukemia. Yang, J.L., Cheng, E.H., Capizzi, R.L., Cheng, Y.C., Kute, T. J. Clin. Invest. (1985) [Pubmed]
  9. 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. Haveman, J., Sigmond, J., van Bree, C., Franken, N.A., Koedooder, C., Peters, G.J. Oncol. Rep. (2006) [Pubmed]
  10. Molecular and biochemical mechanisms of fludarabine and cladribine resistance in a human promyelocytic cell line. Månsson, E., Spasokoukotskaja, T., Sällström, J., Eriksson, S., Albertioni, F. Cancer Res. (1999) [Pubmed]
  11. Immunocytochemical detection of deoxycytidine kinase in pediatric malignancies in relation to in vitro cytarabine sensitivity. Hubeek, I., Peters, G.J., Broekhuizen, A.J., Talianidis, I., Schouten van Meeteren, A.Y., van Wering, E.R., Gibson, B., Creutzig, U., Kaspers, G.J. Nucleosides Nucleotides Nucleic Acids (2004) [Pubmed]
  12. Mechanisms of uptake and resistance to troxacitabine, a novel deoxycytidine nucleoside analogue, in human leukemic and solid tumor cell lines. Gourdeau, H., Clarke, M.L., Ouellet, F., Mowles, D., Selner, M., Richard, A., Lee, N., Mackey, J.R., Young, J.D., Jolivet, J., Lafrenière, R.G., Cass, C.E. Cancer Res. (2001) [Pubmed]
  13. Characterization of resistance to cytosine arabinoside (Ara-C) in NALM-6 human B leukemia cells. Kanno, S., Hiura, T., Ohtake, T., Koiwai, K., Suzuki, H., Ujibe, M., Ishikawa, M. Clin. Chim. Acta (2007) [Pubmed]
  14. Cloning and expression of human deoxyguanosine kinase cDNA. Johansson, M., Karlsson, A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  15. Arabinosylguanine is phosphorylated by both cytoplasmic deoxycytidine kinase and mitochondrial deoxyguanosine kinase. Rodriguez, C.O., Mitchell, B.S., Ayres, M., Eriksson, S., Gandhi, V. Cancer Res. (2002) [Pubmed]
  16. Real-time quantitative PCR assays for deoxycytidine kinase, deoxyguanosine kinase and 5'-nucleotidase mRNA measurement in cell lines and in patients with leukemia. Månsson, E., Liliemark, E., Söderhäll, S., Gustafsson, G., Eriksson, S., Albertioni, F. Leukemia (2002) [Pubmed]
  17. The pattern of deoxycytidine- and deoxyguanosine kinase activity in relation to messenger RNA expression in blood cells from untreated patients with B-cell chronic lymphocytic leukemia. Lotfi, K., Karlsson, K., Fyrberg, A., Juliusson, G., Jonsson, V., Peterson, C., Eriksson, S., Albertioni, F. Biochem. Pharmacol. (2006) [Pubmed]
  18. Role of salvage and phosphorylation in the immunostimulatory activity of C8-substituted guanine ribonucleosides. Goodman, M.G. J. Immunol. (1988) [Pubmed]
  19. Pharmacological basis for cladribine resistance. Lotfi, K., Juliusson, G., Albertioni, F. Leuk. Lymphoma (2003) [Pubmed]
  20. Role of USF1 in the differential expression of the human deoxycytidine kinase gene in acute myeloid leukemia. Ge, Y., Jensen, T.L., Tatman, D.A., Stout, M.L., Buck, S.A., Ravindranath, Y., Matherly, L.H., Taub, J.W. Leukemia (2005) [Pubmed]
  21. Substrate/inhibitor specificities of human deoxycytidine kinase (dCK) and thymidine kinases (TK1 and TK2). Kierdaszuk, B., Krawiec, K., Kazimierczuk, Z., Jacobsson, U., Johansson, N.G., Munch-Petersen, B., Eriksson, S., Shugar, D. Adv. Exp. Med. Biol. (1998) [Pubmed]
  22. Selective increase of dATP pools upon activation of deoxycytidine kinase in lymphocytes: implications in apoptosis. Keszler, G., Spasokoukotskaja, T., Csapo, Z., Virga, S., Staub, M., Sasvari-Szekely, M. Nucleosides Nucleotides Nucleic Acids (2004) [Pubmed]
  23. Human placental deoxyadenosine and deoxyguanosine phosphorylating activity. Hurley, M.C., Palella, T.D., Fox, I.H. J. Biol. Chem. (1983) [Pubmed]
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