title: Tomato thymidine kinase is subject to inefficient TTP feedback regulation.
abstract: A promising suicide gene therapy system to treat gliomas has been reported: the thymidine kinase 1 from tomato (toTK1) combined with the nucleoside analog pro-drug zidovudine (azidothymidine, AZT), which is known to penetrate the blood-brain barrier. Transduction with toTK1 has been found to efficiently increase the sensitivity of human glioblastoma cells to AZT, and nude rats with intracranial glioblastoma grafts have shown significantly improved survival when treated with the toTK1/AZT system. We show in our paper that the strong suicidal effect of AZT together with toTK1 may be explained by reduced TTP-mediated feedback inhibition of the AZT phosphorylation.
authors.affiliation: a Department of Biology , Lund University , Sweden.
authors.forename: N B
authors.initials: NB
authors.lastname: Larsen
authors.forename: B
authors.initials: B
authors.lastname: Munch-Petersen
authors.forename: J
authors.initials: J
authors.lastname: Piškur
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D025461:Feedback, Physiological / Q000187:drug effects*; D006801:Humans; D018551:Solanum lycopersicum / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013942:Thymine Nucleotides / Q000494:pharmacology*; D015215:Zidovudine / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D013942:Thymine Nucleotides; D015215:Zidovudine; D013937:Thymidine Kinase; C092717:thymidine kinase 1; C024157:thymidine 5'-triphosphate
keywords: Antiviral nucleosides; anticancer nucleosides; carcinogenicity; enzyme inhibition; enzymology; gene regulation