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Gene Review

UL23  -  thymidine kinase

Human herpesvirus 1

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Disease relevance of UL23

  • In our current study, we incorporated the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) within pIX to determine if a larger protein of this type could retain functionality in this context [1].
  • The alternative display of HSV-1 TK on the capsid may offer advantages with respect to direct functional applications of this gene product [1].
  • Analysis of cell killing after adenovirus infection showed that the protein IX-TK fusion protein could also serve as a therapeutic gene by rendering transduced cells sensitive to gancyclovir [1].
  • Using an in vitro [3H]-thymidine phosphorylation assay, we demonstrated that the kinase activity of the protein IX-TK fusion protein incorporated into adenoviral virions is functional [1].
  • Gene therapy for treatment of glioma often involves delivery of herpes simplex virus-1 thymidine kinase gene [2].

High impact information on UL23


Chemical compound and disease context of UL23


Biological context of UL23


Anatomical context of UL23


Associations of UL23 with chemical compounds

  • Lobucavir (Cyclobut-G), a ganciclovir analogue, displayed a two- to three-fold more pronounced bystander killer effect than ganciclovir, eliminating, at a concentration of 10 microM, 75% and 90% of a cell population that contained 5% and 10% tk gene-transfected cells, respectively [22].
  • These effects were mRNA specific, as polyribosomal analysis of two cellular transcripts (glyceraldehyde-3-phosphate dehydrogenase and beta-actin) and two early HSV transcripts (thymidine kinase and ICP8) indicated that ICP27 is not required for efficient translation of these mRNAs [23].
  • Compound 26b competitively inhibited TK-2 with respect to thymidine and uncompetitively with respect to ATP [24].
  • N1-substituted thymine derivatives as mitochondrial thymidine kinase (TK-2) inhibitors [24].
  • HSV1 thymidine kinase phosphorylates the primary hydroxyl of both the R and the S isomers of iNDG [25].

Other interactions of UL23


Analytical, diagnostic and therapeutic context of UL23


  1. Genetic incorporation of HSV-1 thymidine kinase into the adenovirus protein IX for functional display on the virion. Li, J., Le, L., Sibley, D.A., Mathis, J.M., Curiel, D.T. Virology (2005) [Pubmed]
  2. Inflammatory thoughts about glioma gene therapy. Kielian, T., Hickey, W.F. Nat. Med. (1999) [Pubmed]
  3. The relationship of IL-4- and IFN gamma-producing T cells studied by lineage ablation of IL-4-producing cells. Kamogawa, Y., Minasi, L.A., Carding, S.R., Bottomly, K., Flavell, R.A. Cell (1993) [Pubmed]
  4. Murine genomic DNA sequences replicating autonomously in mouse L cells. Holst, A., Müller, F., Zastrow, G., Zentgraf, H., Schwender, S., Dinkl, E., Grummt, F. Cell (1988) [Pubmed]
  5. Evidence for intrachromosomal gene conversion in cultured mouse cells. Liskay, R.M., Stachelek, J.L. Cell (1983) [Pubmed]
  6. Chronic brain inflammation and persistent herpes simplex virus 1 thymidine kinase expression in survivors of syngeneic glioma treated by adenovirus-mediated gene therapy: implications for clinical trials. Dewey, R.A., Morrissey, G., Cowsill, C.M., Stone, D., Bolognani, F., Dodd, N.J., Southgate, T.D., Klatzmann, D., Lassmann, H., Castro, M.G., Löwenstein, P.R. Nat. Med. (1999) [Pubmed]
  7. Germline transmission of exogenous genes in the chicken. Bosselman, R.A., Hsu, R.Y., Boggs, T., Hu, S., Bruszewski, J., Ou, S., Kozar, L., Martin, F., Green, C., Jacobsen, F. Science (1989) [Pubmed]
  8. Transcription of the simian virus 40 genome in DNA-transformed murine teratocarcinoma stem cells. Linnenbach, A., Huebner, K., Croce, C.M. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  9. Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice. Feldman, L.T., Ellison, A.R., Voytek, C.C., Yang, L., Krause, P., Margolis, T.P. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  10. Crystal structures of the thymidine kinase from herpes simplex virus type-1 in complex with deoxythymidine and ganciclovir. Brown, D.G., Visse, R., Sandhu, G., Davies, A., Rizkallah, P.J., Melitz, C., Summers, W.C., Sanderson, M.R. Nat. Struct. Biol. (1995) [Pubmed]
  11. Minimal transcriptional enhancer of simian virus 40 is a 74-base-pair sequence that has interacting domains. Firak, T.A., Subramanian, K.N. Mol. Cell. Biol. (1986) [Pubmed]
  12. The alpha promoter regulator-ovalbumin chimeric gene resident in human cells is regulated like the authentic alpha 4 gene after infection with herpes simplex virus 1 mutants in alpha 4 gene. Herz, C., Roizman, B. Cell (1983) [Pubmed]
  13. A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography. Gambhir, S.S., Bauer, E., Black, M.E., Liang, Q., Kokoris, M.S., Barrio, J.R., Iyer, M., Namavari, M., Phelps, M.E., Herschman, H.R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  14. Creation of drug-specific herpes simplex virus type 1 thymidine kinase mutants for gene therapy. Black, M.E., Newcomb, T.G., Wilson, H.M., Loeb, L.A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  15. Determination of mRNA fate by different RNA polymerase II promoters. Enssle, J., Kugler, W., Hentze, M.W., Kulozik, A.E. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  16. Chemically induced mutagenesis in a shuttle vector with a low-background mutant frequency. Drinkwater, N.R., Klinedinst, D.K. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  17. Two-step transcriptional amplification as a method for imaging reporter gene expression using weak promoters. Iyer, M., Wu, L., Carey, M., Wang, Y., Smallwood, A., Gambhir, S.S. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  18. Targeting of an inducible toxic phenotype in animal cells. Borrelli, E., Heyman, R., Hsi, M., Evans, R.M. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  19. Genetic ablation of parietal cells in transgenic mice: a new model for analyzing cell lineage relationships in the gastric mucosa. Canfield, V., West, A.B., Goldenring, J.R., Levenson, R. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  20. Glucocorticoid regulation of mouse mammary tumor virus sequences in transgenic mice. Ross, S.R., Solter, D. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  21. High-frequency transfer of cloned herpes simplex virus type 1 sequences to mammalian cells by protoplast fusion. Sandri-Goldin, R.M., Goldin, A.L., Levine, M., Glorioso, J.C. Mol. Cell. Biol. (1981) [Pubmed]
  22. Bystander effect of purine nucleoside analogues in HSV-1 tk suicide gene therapy is superior to that of pyrimidine nucleoside analogues. Degrève, B., De Clercq, E., Balzarini, J. Gene Ther. (1999) [Pubmed]
  23. Control of VP16 translation by the herpes simplex virus type 1 immediate-early protein ICP27. Ellison, K.S., Maranchuk, R.A., Mottet, K.L., Smiley, J.R. J. Virol. (2005) [Pubmed]
  24. 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]
  25. Enzymatic phosphorylation of the antiherpetic agent 9-[(2,3-dihydroxy-1-propoxy)methyl]guanine. Karkas, J.D., Ashton, W.T., Canning, L.F., Liou, R., Germershausen, J., Bostedor, R., Arison, B., Field, A.K., Tolman, R.L. J. Med. Chem. (1986) [Pubmed]
  26. Herpes simplex virus type 1 UL46 and UL47 deletion mutants lack VP11 and VP12 or VP13 and VP14, respectively, and exhibit altered viral thymidine kinase expression. Zhang, Y., McKnight, J.L. J. Virol. (1993) [Pubmed]
  27. The product of the UL31 gene of herpes simplex virus 1 is a nuclear phosphoprotein which partitions with the nuclear matrix. Chang, Y.E., Roizman, B. J. Virol. (1993) [Pubmed]
  28. Intercellular trafficking and cytotoxicity of recombinant HSV-1 thymidine kinase fused with HSV-2 US11 RXP repeat peptide. Luo, C., Nawa, A., Yamauchi, Y., Kohno, S., Ushijima, Y., Goshima, F., Kikkawa, F., Nishiyama, Y. Virus Genes (2007) [Pubmed]
  29. Sequential switching of DNA polymerase and thymidine kinase-mediated HSV-1 drug resistance in an immunocompromised child. Stránská, R., van Loon, A.M., Bredius, R.G., Polman, M., Nienhuis, E., Beersma, M.F., Lankester, A.C., Schuurman, R. Antivir. Ther. (Lond.) (2004) [Pubmed]
  30. The Epstein-Barr virus (EBV) early promoter DR contains a cis-acting element responsive to the EBV transactivator EB1 and an enhancer with constitutive and inducible activities. Chavrier, P., Gruffat, H., Chevallier-Greco, A., Buisson, M., Sergeant, A. J. Virol. (1989) [Pubmed]
  31. Therapy of colon cancer with oncolytic adenovirus is enhanced by the addition of herpes simplex virus-thymidine kinase. Wildner, O., Blaese, R.M., Morris, J.C. Cancer Res. (1999) [Pubmed]
  32. Folding and self-assembly of herpes simplex virus type 1 thymidine kinase. Wurth, C., Thomas, R.M., Folkers, G., Scapozza, L. J. Mol. Biol. (2001) [Pubmed]
  33. MicroPET imaging of Cre-loxP-mediated conditional activation of a herpes simplex virus type 1 thymidine kinase reporter gene. Sundaresan, G., Paulmurugan, R., Berger, F., Stiles, B., Nagayama, Y., Wu, H., Gambhir, S.S. Gene Ther. (2004) [Pubmed]
  34. T-Cell suicide gene therapy for organ transplantation: induction of long-lasting tolerance to allogeneic heart without generalized immunosuppression. Braunberger, E., Cohen, J.L., Boyer, O., Pegaz-Fiornet, B., Raynal-Raschilas, N., Bruneval, P., Thomas-Vaslin, V., Bellier, B., Carpentier, A., Glotz, D., Klatzmann, D. Mol. Ther. (2000) [Pubmed]
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