Thymidine kinase 1
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]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Fluorouracil (5-FU) Activity edit
- ↑ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".
Cancer detection
Thymidine kinase has been making a growing impact in the cancer research community. It has been found that elevated blood serum levels of TK-1 correlates with metastatic capabilities of the cancer and thereby can be used to detect malignant types of cancer, furthermore TK-1 has been found to show up in blood serum even before clinical symptoms even start to show.[3] This would allow quicker treatment before the cancer becomes too developed. TK-1 has also been found to correlate with the return of breast cancer along with many more types of cancer.[4] TK-1 can be used to detect cancer earlier, determine what stage it is in, and if in remission it can be used to predict another cancer growth event. Attempts to make commercial ELISA tests to test blood serum levels have not been promising.
References
- ↑ "Entrez Gene: Thymidine kinase 1, soluble".
- ↑ Huang DY, Chang ZF (June 2001). "Interaction of human thymidine kinase 1 with p21(Waf1)". Biochem. J. 356 (Pt 3): 829–34. doi:10.1042/0264-6021:3560829. PMC 1221910. PMID 11389691.
- ↑ Alegre MM, Robison RA, O'Neill KL (May 2013). "Thymidine Kinase 1: A Universal Marker for Cancer". Cancer and Clinical Oncology 2 (1). doi:10.5539/cco.v2n1p159.
- ↑ Alegre MM, Robison RA, O'Neill KL (2012). "Thymidine kinase 1 upregulation is an early event in breast tumor formation". Journal of Oncology 2012: 575647. doi:10.1155/2012/575647. PMC 3388419. PMID 22778736.
Further reading
- Kim YK, Lee AS (1992). "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. PMID 1370831.
- Barik S, Banerjee AK (1991). "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. PMC 239976. PMID 1848304.
- Sadava D, Bernard B (1990). "Transition from cytosolic to mitochondrial thymidine kinase during development in human fetal tissues". Life Sci. 47 (25): 2359–64. doi:10.1016/0024-3205(90)90275-V. PMID 2263164.
- Tamiya N, Yusa T, Yamaguchi Y, Tsukifuji R, Kuroiwa N, Moriyama Y, Fujimura S (1989). "Co-purification of thymidylate kinase and cytosolic thymidine kinase from human term placenta by affinity chromatography". Biochim. Biophys. Acta 995 (1): 28–35. doi:10.1016/0167-4838(89)90229-X. PMID 2538159.
- Slagel V, Flemington E, Traina-Dorge V, Bradshaw H, Deininger P (1987). "Clustering and subfamily relationships of the Alu family in the human genome". Mol. Biol. Evol. 4 (1): 19–29. PMID 3128713.
- Flemington E, Bradshaw HD, Traina-Dorge V, Slagel V, Deininger PL (1987). "Sequence, structure and promoter characterization of the human thymidine kinase gene". Gene 52 (2-3): 267–77. doi:10.1016/0378-1119(87)90053-9. PMID 3301530.
- Sherley JL, Kelly TJ (1988). "Human cytosolic thymidine kinase. Purification and physical characterization of the enzyme from HeLa cells". J. Biol. Chem. 263 (1): 375–82. PMID 3335503.
- Kreidberg JA, Kelly TJ (1986). "Genetic analysis of the human thymidine kinase gene promoter". Mol. Cell. Biol. 6 (8): 2903–9. PMC 367858. PMID 3785218.
- Bradshaw HD, Deininger PL (1984). "Human thymidine kinase gene: molecular cloning and nucleotide sequence of a cDNA expressible in mammalian cells". Mol. Cell. Biol. 4 (11): 2316–20. PMC 369060. PMID 6549046.
- Kuo WL, Hirschhorn R, Huie ML, Hirschhorn K (1996). "Localization and ordering of acid alpha-glucosidase (GAA) and thymidine kinase (TK1) by fluorescence in situ hybridization". Hum. Genet. 97 (3): 404–6. doi:10.1007/BF02185782. PMID 8786092.
- Chang ZF, Huang DY, Chi LM (1998). "Serine 13 is the site of mitotic phosphorylation of human thymidine kinase". J. Biol. Chem. 273 (20): 12095–100. doi:10.1074/jbc.273.20.12095. PMID 9575153.
- Berenstein D, Christensen JF, Kristensen T, Hofbauer R, Munch-Petersen B (2000). "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. doi:10.1074/jbc.M005325200. PMID 10924519.
- Huang DY, Chang ZF (2001). "Interaction of human thymidine kinase 1 with p21(Waf1)". Biochem. J. 356 (Pt 3): 829–34. doi:10.1042/0264-6021:3560829. PMC 1221910. PMID 11389691.
- Fujiwaki R, Hata K, Moriyama M, Iwanari O, Katabuchi H, Okamura H, Miyazaki K (2001). "Clinical value of thymidine kinase in patients with cervical carcinoma". Oncology 61 (1): 47–54. doi:10.1159/000055352. PMID 11474248.
- Fujiwaki R, Hata K, Nakayama K, Moriyama M, Iwanari O, Katabuchi H, Okamura H, Sakai E, Miyazaki K (2002). "Thymidine kinase in epithelial ovarian cancer: relationship with the other pyrimidine pathway enzymes". Int. J. Cancer 99 (3): 328–35. doi:10.1002/ijc.10319. PMID 11992400.
- Mao Y, Wu J, Wang N, He L, Wu C, He Q, Skog S (2002). "A comparative study: immunohistochemical detection of cytosolic thymidine kinase and proliferating cell nuclear antigen in breast cancer". Cancer Invest. 20 (7-8): 922–31. doi:10.1081/CNV-120005905. PMID 12449723.
- Gilles SI, Romain S, Casellas P, Ouafik L, Fina F, Combes T, Vuaroquaux V, Seitz JF, Bonnier P, Galiègue S, Carayon P, Martin PM (2003). "Mutation analysis in the coding sequence of thymidine kinase 1 in breast and colorectal cancer". Int. J. Biol. Markers 18 (1): 1–6. PMID 12699056.
- Han T, Fernandez M, Sarkar M, Agarwal RP (2004). "2', 3'-Dideoxycytidine represses thymidine kinases 1 and 2 expression in T-lymphoid cells". Life Sci. 74 (7): 835–42. doi:10.1016/j.lfs.2003.07.023. PMID 14659972.
- Li CL, Lu CY, Ke PY, Chang ZF (2004). "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. doi:10.1016/j.bbrc.2003.11.147. PMID 14697231.
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