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Gene Review

dnk  -  deoxyribonucleoside kinase

Drosophila melanogaster

Synonyms: CG5452, DM-dNK, DNK, Deoxynucleoside kinase, Deoxyribonucleoside kinase, ...
 
 
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Disease relevance of dnk

 

High impact information on dnk

 

Chemical compound and disease context of dnk

 

Biological context of dnk

 

Anatomical context of dnk

  • We have recently shown that the overexpression of Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK) in cancer cell lines increases the cells' sensitivity to several cytotoxic nucleoside analogs and the enzyme may accordingly be used as a suicide gene in combined gene/chemotherapy treatment of cancer [9].
  • In summary, we showed that the cells' sensitivity and the efficiency of bystander cell killing were not dependent on whether Dm-dNK was located in the nucleus or cytosol [9].
  • We showed that Dm-dNK can be expressed in human cells, that the enzyme retained its enzymatic activity, and that it is localized in the cell nuclei due to a nuclear localization signal in its C-terminal region [10].
  • The Drosophila melanogaster deoxynucleoside kinase gene was introduced into HeLa cells with cationic lipids to allow its transient expression, and cytotoxic effects of several nucleoside analogs in the transfected cells were examined [11].
 

Associations of dnk with chemical compounds

 

Analytical, diagnostic and therapeutic context of dnk

  • The cDNA cloning and characterization of Dm-dNK will be the basis for studies on the use of this multisubstrate nucleoside kinase as a suicide gene in combined gene/chemotherapy of cancer [1].
  • The detailed picture of the structure-function relationship provides an improved background for future development of novel mutant suicide genes for Dm-dNK-mediated gene therapy [15].

References

  1. Cloning and characterization of the multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster. Johansson, M., van Rompay, A.R., Degrève, B., Balzarini, J., Karlsson, A. J. Biol. Chem. (1999) [Pubmed]
  2. Gemcitabine resistance due to deoxycytidine kinase deficiency can be reverted by fruitfly deoxynucleoside kinase, DmdNK, in human uterine sarcoma cells. Jordheim, L.P., Galmarini, C.M., Dumontet, C. Cancer Chemother. Pharmacol. (2006) [Pubmed]
  3. A few amino acid substitutions can convert deoxyribonucleoside kinase specificity from pyrimidines to purines. Knecht, W., Sandrini, M.P., Johansson, K., Eklund, H., Munch-Petersen, B., Piskur, J. EMBO J. (2002) [Pubmed]
  4. DNA of Drosophila melanogaster contains 5-methylcytosine. Gowher, H., Leismann, O., Jeltsch, A. EMBO J. (2000) [Pubmed]
  5. N1-substituted thymine derivatives as mitochondrial thymidine kinase (TK-2) inhibitors. Hernandez, A.I., Familiar, O., Negri, A., Rodríguez-Barrios, F., Gago, F., Karlsson, A., Camarasa, M.J., Balzarini, J., Pérez-Pérez, M.J. J. Med. Chem. (2006) [Pubmed]
  6. Active site mutants of Drosophila melanogaster multisubstrate deoxyribonucleoside kinase. Solaroli, N., Bjerke, M., Amiri, M.H., Johansson, M., Karlsson, A. Eur. J. Biochem. (2003) [Pubmed]
  7. Bystander effects of cancer cell lines transduced with the multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster and synergistic enhancement by hydroxyurea. Zheng, X., Johansson, M., Karlsson, A. Mol. Pharmacol. (2001) [Pubmed]
  8. Enhanced toxicity of purine nucleoside analogs in cells expressing Drosophila melanogaster nucleoside kinase mutants. Solaroli, N., Johansson, M., Balzarini, J., Karlsson, A. Gene Ther. (2007) [Pubmed]
  9. Nucleoside analog cytotoxicity and bystander cell killing of cancer cells expressing Drosophila melanogaster deoxyribonucleoside kinase in the nucleus or cytosol. Zheng, X., Johansson, M., Karlsson, A. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  10. Retroviral transduction of cancer cell lines with the gene encoding Drosophila melanogaster multisubstrate deoxyribonucleoside kinase. Zheng, X., Johansson, M., Karlsson, A. J. Biol. Chem. (2000) [Pubmed]
  11. Transient expression of Drosophila melanogaster deoxynucleoside kinase gene enhances cytotoxicity of nucleoside analogs. Kamiya, H., Ochiai, H., Harashima, H., Ito, M., Matsuda, A. Nucleosides Nucleotides Nucleic Acids (2006) [Pubmed]
  12. The Drosophila melanogaster UMP-CMP kinase cDNA encodes an N-terminal mitochondrial import signal. Curbo, S., Amiri, M., Foroogh, F., Johansson, M., Karlsson, A. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  13. The multifunctional deoxynucleoside kinase of insect cells is a target for the development of new insecticides. Balzarini, J., Degrève, B., Hatse, S., De Clercq, E., Breuer, M., Johansson, M., Huybrechts, R., Karlsson, A. Mol. Pharmacol. (2000) [Pubmed]
  14. Deoxyribonucleoside kinases belonging to the thymidine kinase 2 (TK2)-like group vary significantly in substrate specificity, kinetics and feed-back regulation. Knecht, W., Petersen, G.E., Munch-Petersen, B., Piskur, J. J. Mol. Biol. (2002) [Pubmed]
  15. Structural basis for the changed substrate specificity of Drosophila melanogaster deoxyribonucleoside kinase mutant N64D. Welin, M., Skovgaard, T., Knecht, W., Zhu, C., Berenstein, D., Munch-Petersen, B., Piskur, J., Eklund, H. FEBS J. (2005) [Pubmed]
  16. Structural basis for substrate specificities of cellular deoxyribonucleoside kinases. Johansson, K., Ramaswamy, S., Ljungcrantz, C., Knecht, W., Piskur, J., Munch-Petersen, B., Eriksson, S., Eklund, H. Nat. Struct. Biol. (2001) [Pubmed]
 
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