Thymidine kinase 1 explained

Thymidine kinase 1, soluble (gene name TK1), is a human thymidine kinase.^[1]

Two forms of this protein have been identified in animal cells, one in cytosol and one in mitochondria. Activity of the cytosolic enzyme is high in proliferating cells and peaks during the S-phase of the cell cycle; it is very low in resting cells.

Interactions

Thymidine kinase 1 has been shown to interact with P21.^[2]

Thymidine Kinase 1 in Cancer

Elevations in serum TK-1 have been found to correlate with the return of breast and other forms of cancer^[3] TK-1 can be used to detect cancer earlier, determine what stage it is in, and detect recurrence. Thymidine Kinase 1 can be measured based on its enzyme activity^[4] or using immunoassay.^[5]

Further reading

• Kim YK, Lee AS . Identification of a protein-binding site in the promoter of the human thymidine kinase gene required for the G1-S-regulated transcription . J. Biol. Chem. . 267 . 4 . 2723–7 . 1992 . 10.1016/S0021-9258(18)45939-X . 1370831 . free .
• Barik S, Banerjee AK . Cloning and expression of the vesicular stomatitis virus phosphoprotein gene in Escherichia coli: analysis of phosphorylation status versus transcriptional activity . J. Virol. . 65 . 4 . 1719–26 . 1991 . 1848304 . 239976 . 10.1128/JVI.65.4.1719-1726.1991.
• Sadava D, Bernard B . Transition from cytosolic to mitochondrial thymidine kinase during development in human fetal tissues . Life Sci. . 47 . 25 . 2359–64 . 1990 . 2263164 . 10.1016/0024-3205(90)90275-V .
• Tamiya N, Yusa T, Yamaguchi Y, Tsukifuji R, Kuroiwa N, Moriyama Y, Fujimura S . Co-purification of thymidylate kinase and cytosolic thymidine kinase from human term placenta by affinity chromatography . Biochim. Biophys. Acta . 995 . 1 . 28–35 . 1989 . 2538159 . 10.1016/0167-4838(89)90229-X .
• Slagel V, Flemington E, Traina-Dorge V, Bradshaw H, Deininger P . Clustering and subfamily relationships of the Alu family in the human genome . Mol. Biol. Evol. . 4 . 1 . 19–29 . 1987 . 3128713 . 10.1093/oxfordjournals.molbev.a040422. free .
• Flemington E, Bradshaw HD, Traina-Dorge V, Slagel V, Deininger PL . Sequence, structure and promoter characterization of the human thymidine kinase gene . Gene . 52 . 2–3 . 267–77 . 1987 . 3301530 . 10.1016/0378-1119(87)90053-9 .
• Sherley JL, Kelly TJ . Human cytosolic thymidine kinase. Purification and physical characterization of the enzyme from HeLa cells . J. Biol. Chem. . 263 . 1 . 375–82 . 1988 . 10.1016/S0021-9258(19)57403-8 . 3335503 . free .
• Kreidberg JA, Kelly TJ . Genetic analysis of the human thymidine kinase gene promoter . Mol. Cell. Biol. . 6 . 8 . 2903–9 . 1986 . 3785218 . 367858 . 10.1128/mcb.6.8.2903.
• Bradshaw HD, Deininger PL . Human thymidine kinase gene: molecular cloning and nucleotide sequence of a cDNA expressible in mammalian cells . Mol. Cell. Biol. . 4 . 11 . 2316–20 . 1984 . 6549046 . 369060 . 10.1128/mcb.4.11.2316.
• Kuo WL, Hirschhorn R, Huie ML, Hirschhorn K . Localization and ordering of acid alpha-glucosidase (GAA) and thymidine kinase (TK1) by fluorescence in situ hybridization . Hum. Genet. . 97 . 3 . 404–6 . 1996 . 8786092 . 10.1007/BF02185782 . 9056186 .
• Chang ZF, Huang DY, Chi LM . Serine 13 is the site of mitotic phosphorylation of human thymidine kinase . J. Biol. Chem. . 273 . 20 . 12095–100 . 1998 . 9575153 . 10.1074/jbc.273.20.12095 . free .
• Berenstein D, Christensen JF, Kristensen T, Hofbauer R, Munch-Petersen B . Valine, not methionine, is amino acid 106 in human cytosolic thymidine kinase (TK1). Impact on oligomerization, stability, and kinetic properties . J. Biol. Chem. . 275 . 41 . 32187–92 . 2000 . 10924519 . 10.1074/jbc.M005325200 . free .
• Huang DY, Chang ZF . Interaction of human thymidine kinase 1 with p21(Waf1) . Biochem. J. . 356 . Pt 3 . 829–34 . 2001 . 11389691 . 1221910 . 10.1042/0264-6021:3560829 .
• Fujiwaki R, Hata K, Moriyama M, Iwanari O, Katabuchi H, Okamura H, Miyazaki K . Clinical value of thymidine kinase in patients with cervical carcinoma . Oncology . 61 . 1 . 47–54 . 2001 . 11474248 . 10.1159/000055352 . 9006108 .
• Fujiwaki R, Hata K, Nakayama K, Moriyama M, Iwanari O, Katabuchi H, Okamura H, Sakai E, Miyazaki K . Thymidine kinase in epithelial ovarian cancer: relationship with the other pyrimidine pathway enzymes . Int. J. Cancer . 99 . 3 . 328–35 . 2002 . 11992400 . 10.1002/ijc.10319 . 23856606 . free .
• Mao Y, Wu J, Wang N, He L, Wu C, He Q, Skog S . A comparative study: immunohistochemical detection of cytosolic thymidine kinase and proliferating cell nuclear antigen in breast cancer . Cancer Invest. . 20 . 7–8 . 922–31 . 2002 . 12449723 . 10.1081/CNV-120005905 . 23072666 .
• Gilles SI, Romain S, Casellas P, Ouafik L, Fina F, Combes T, Vuaroquaux V, Seitz JF, Bonnier P, Galiègue S, Carayon P, Martin PM . Mutation analysis in the coding sequence of thymidine kinase 1 in breast and colorectal cancer . Int. J. Biol. Markers . 18 . 1 . 1–6 . 2003 . 12699056 . 10.5301/jbm.2008.2452.
• Han T, Fernandez M, Sarkar M, Agarwal RP . 2', 3'-Dideoxycytidine represses thymidine kinases 1 and 2 expression in T-lymphoid cells . Life Sci. . 74 . 7 . 835–42 . 2004 . 14659972 . 10.1016/j.lfs.2003.07.023 .
• Li CL, Lu CY, Ke PY, Chang ZF . Perturbation of ATP-induced tetramerization of human cytosolic thymidine kinase by substitution of serine-13 with aspartic acid at the mitotic phosphorylation site . Biochem. Biophys. Res. Commun. . 313 . 3 . 587–93 . 2004 . 14697231 . 10.1016/j.bbrc.2003.11.147 .
• ONeill KL, Buckwalter M, Murray BK . Thymidine kinase: diagnostic and prognostic potential . Expert Rev. Mol. Diagn. . 1 . 4 . 428–33 . 2001 . 11901857 . 10.1586/14737159.1.4.428. 12790327 .
• Topolcan O, Holubec Jr L . The role of thymidine kinase in cancer diseases . Expert Opin. Med. Diagn. . 2 . 2 . 129–41 . 2008 . 23485133 . 10.1517/17530059.2.2.129 .
• Jagarlamudi KK, Shaw M . Thymidine Kinase 1 as a Tumor Biomarker: Technical Advances offer New Potential to an Old Biomarker . Biomark. Med. . 12 . 9 . 1035–48 . 2018 . 30039979 . 10.2217/bmm-2018-0157 . free .

Notes and References

1. Web site: Entrez Gene: Thymidine kinase 1, soluble.
2. Huang DY, Chang ZF . Interaction of human thymidine kinase 1 with p21(Waf1) . Biochem. J. . 356 . Pt 3 . 829–34 . June 2001 . 11389691 . 1221910 . 10.1042/0264-6021:3560829 .
3. Alegre MM, Robison RA, O'Neill KL . Thymidine kinase 1 up-regulation is an early event in breast tumor formation . Journal of Oncology . 2012 . 575647 . 2012 . 22778736 . 3388419 . 10.1155/2012/575647 . free .
4. Munch-Petersen B . Differences in the kinetic properties of thymidine kinase isoenzymes in unstimulated and phytohemagglutinin-stimulated human lymphocytes. . Mol. Cell. Biochem.. 64 . 2 . 1013–19 . 2005 . 10.1007/BF00224774 . 6504022 . 11326439 .
5. He Q, Zhang P, Zou L et al . Concentration of thymidine kinase 1 in serum (S-TK1) is a more sensitive proliferation marker in human solid tumors than its activity. . Oncol. Rep. . 14 . 4 . 1013–19 . 2005 . 16142366 .