Mammalian deoxyribonucleoside kinases

https://doi.org/10.1016/0163-7258(95)00015-9Get rights and content

Abstract

The mammalian deoxyribonucleoside kinases are deoxycytidine kinase, thymidine kinase 1 and 2 and deoxyguanosine kinase. These enzymes phosphorylate deoxyribonucleosides and thereby provide an alternative to de novo synthesis of DNA precursors. Their activities are essential for the activation of several chemotherapeutically important nucleoside analogues. In recent years, these enzymes have been thoroughly characterised with regard to structure, substrate specificity and patterns of expression. In this review, these results are reviewed and furthermore, the physiologic metabolic role of the anabolic enzymes is discussed in relation to catabolic pathways. The significance of this information for the development of therapeutic protocols and choice of animal model systems is discussed. Finally, alternative pathways for nucleoside analogue phosphorylation are surveyed, such as the phosphotransfer capacity of 5′-nucleotidase.

References (218)

  • V. Bianchi et al.

    Effects of mutational loss of nucleoside kinases on deoxyadenosine 5′-phosphate/deoxyadenosine substrate cycles in cultured CEM and V79 cells

    J. Biol. Chem.

    (1994)
  • Z.-F. Chang et al.

    The regulation of thymidine kinase in HL-60 human promyeloleukemia cells

    J. Biol. Chem.

    (1993)
  • C.H. Chen et al.

    The role of cytoplasmic deoxycytidine kinase in the mitochondrial effects of the antihuman immunodeficiency virus compound, 2′,3′-dideoxycytidine

    J. Biol. Chem.

    (1992)
  • A. Cohen et al.

    Purine and pyrimidine metabolism in human T lymphocytes. Regulation of deoxyribonucleotide metabolism

    J. Biol. Chem.

    (1983)
  • A.H. Cory et al.

    Deoxyguanosine-resistant leukemia L1210 cells. Loss of specific deoxyribonucleoside kinase activity

    J. Biol. Chem.

    (1993)
  • N.S. Datta et al.

    Kinetic properties and inhibition of human T lymphoblast deoxycytidine kinase

    J. Biol. Chem.

    (1989)
  • Q.-P. Dou et al.

    Cyclin D1/cdk2 kinase is present in a G1 phase-specific protein complex YI1 that binds to the moust thymidine kinase gene promotor

    Biochem. Biophys. Res. Commun.

    (1994)
  • P.H. Ellims et al.

    Human liver thymidine kinase. Purification and some properties of the enzyme

    J. Biol. Chem.

    (1980)
  • Y. Engström et al.

    Cell cycle-dependent expression of mammalian ribonucleotide reductase. Differential regulation of the two subunits

    J. Biol. Chem.

    (1985)
  • S. Eriksson et al.

    Cell cycle-dependent regulation of mammalian ribonucleotide reductase. The S phase-correlated increase in subunit M2 is regulated by de novo protein synthesis

    J. Biol. Chem.

    (1984)
  • S. Eriksson et al.

    Characterization of human deoxycytidine kinase. Correlation with cDNA sequences

    FEBS Lett.

    (1991)
  • S. Eriksson et al.

    Comparison of the substrate specificities of human thymidine kinase 1 and 2 and deoxycytidine kinase toward antiviral and cytostatic nucleoside analogs

    Biochem. Biophys. Res. Commun.

    (1991)
  • P. Fritzson

    Nucleotidase activities in the soluble fraction of rat liver homogenate

    Biochim. Biophys. Acta

    (1969)
  • P. Fritzson et al.

    A new nucleotidase of rat liver with activity toward 3′- and 5′-nucleotides

    Biochim. Biophys. Acta

    (1971)
  • G.A. Gentry

    Viral thymidine kinases and their relatives

    Pharmacol. Ther.

    (1992)
  • W.J. Gower et al.

    Deoxyguanosine kinase. Distinct molecular forms in mitochondria and cytosol

    J. Biol. Chem.

    (1979)
  • A. Habteyesus et al.

    Deoxynucleoside phosphorylating enzymes in monkey and human tissues show great similarities, while mouse deoxycytidine kinase has a different substrate specificity

    Biochem. Pharmacol.

    (1991)
  • M. Hengstschläger et al.

    Cell cycle regulation of deoxycytidine kinase: evidences for post-transcriptional control

    FEBS Lett.

    (1993)
  • M.S. Hershfield et al.

    Effects of mutational loss of adenosine kinase and deoxycytidine kinase on deoxyATP accumulation and deoxyadenosine toxicity in cultured CEM human T-lymphoblastoid cells

    J. Biol. Chem.

    (1982)
  • L. Höglund et al.

    Cytoplasmic 5′(3′)-nucleotidase from human placenta

    J. Biol. Chem.

    (1990)
  • L. Höglund et al.

    Nucleotidase activities in soluble and membrane fractions of three different mammalian cell lines

    Exp. Cell Res.

    (1990)
  • A. Hrabák et al.

    The salvage of deoxycytidine into dCDP-diacylglycerol by macrophages and lymphocytes

    Biochem. Biophys. Res. Comm.

    (1993)
  • S.-H. Huang et al.

    Human deoxycytidine kinase. Sequence of cDNA clones and analysis of expression in cell lines with and without enzyme activity

    J. Biol. Chem.

    (1989)
  • S.-H. Huang et al.

    Correction. Human deoxycytidine kinase. Sequence of cDNA clones and analysis of expression in cell lines with and without enzyme activity

    J. Biol. Chem.

    (1991)
  • M.C. Hurley et al.

    Human placental deoxyadenosine and deoxyguanosine phosphorylating activity

    J. Biol. Chem.

    (1983)
  • M.C. Hurley et al.

    Regulation of deoxyadenosine and nucleoside analog phosphorylation by human placental adenosine kinase

    J. Biol. Chem.

    (1985)
  • R. Itoh

    Purification and some properties of cytosol 5′-nucleotidase from rat liver

    Biochim. Biophys. Acta

    (1981)
  • R. Itoh

    Studies on some molecular properties of cytosol 5′-nucleotidase from rat liver

    Biochim. Biophys. Acta

    (1982)
  • R. Itoh

    IMP-GMP 5′-nucleotidase from rat liver

    Comp. Biochem. Physiol.

    (1993)
  • D.H. Ives et al.

    Deoxycytidine kinase. III. Kinetics and allosteric regulation of the calf thymus enzyme

    J. Biol. Chem.

    (1970)
  • M.A. Johnson et al.

    2′,3′-Dideoxynucleoside phsophorylation by deoxycytidine kinase from normal human thymus extracts: activation of potential drugs for AIDS therapy

    Biochem. Biophys. Res. Commun.

    (1987)
  • M.A. Johnson et al.

    Metabolic pathways for the activation of the antiretroviral agent 2′,3′-dideoxyadenosine in human lymphoid cells

    J. Biol. Chem.

    (1988)
  • E.S.J. Arnér

    Studies of the salvage and metabolism of deoxyribonucleosides in human cells and tissue

  • E.S.J. Arnér

    Salvage and catabolism of pyrimidine deoxyribonucleosides in monocyte-derived macrophages as compared to mitogen-stimulated peripheral blood mononuclear cells

    Int. Antiv. News

    (1994)
  • E.S.J. Arnér et al.

    Phosphorylation of 2-chlorodeoxyadenosine (CdA) in peripheral blood mononuclear cells of leukaemia patients

    Br. J. Haematol.

    (1994)
  • B. Aronow et al.

    Mutant mouse cells with nitrobenzylthioinosine-insensitive nucleoside transport functions

    Adv. Exp. Med. Biol.

    (1986)
  • G. Attardi et al.

    Biogenesis of mitochondria

    Annu. Rev. Cell Biol.

    (1988)
  • D.P. Baccanari et al.

    5-Ethynyluracil (776C85): a potent modulator of the pharmacokinetics and antitumor efficasy of 5-fluorouracil

  • J. Balzarini et al.

    The anti-HTLV-III (anti-HIV) and cytotoxic activity of 2′,3′-didehydro-2′,3′-dideoxyribonucleosides: a comparison with their parental 2′,3′-dideoxyribonucleosides

    Mol. Pharmacol.

    (1987)
  • L.L. Bennett et al.

    Phosphorylation of the enantiomers of the carbocyclic analog of 2′-deoxyguanosine in cells infected with herpes simplex virus type 1 and in uninfected cells. Lack of enantiomeric selectivity with the viral thymidine kinase

    Mol. Pharmacol.

    (1993)
  • Cited by (530)

    • Imaging the immune cell in immunotherapy

      2022, NK Cells in Cancer Immunotherapy: Successes and Challenges
    View all citing articles on Scopus

    Parts of this review are based on the thesis, “Studies of the Salvage and Metabolism of Deoxyribonucleosides in Human Cells and Tissues,” by Elias S. J. Arnér, 1993, Karolinska Institut, Stockholm, ISBN 91-628-0984-9.

    View full text