Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.1.21 (thymidine kinase)
7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of dietary zinc levels on DNA synthesis in transplanted hepatomas induced by 3'-methyl-4-dimethyl-amino-azobenzene was investigated. DNA synthesis was found to be reduced (P less than 0,01) in rats maintained on diets low in zinc (0,5 mug/g) and high in zinc (less than 500 mug/g) when compared with the control animals given 60 mug zinc/g ration. Subsequently, the effect of dietary zinc intakes on the activity of 2 zinc-dependent enzymes associated with DNA synthesis--thymidine kinase and DNA polymerase--was studied. Both thymidine kinase and DNA polymerase activity was significantly reduced in animals receiving the zinc-deficient (0,5 mug/g) and zinc-supplemented (less than 500 mug/g) diets when compared with the control animals (60 mug/g). The data indicated that the DNA synthesis was the primary locus associated with zinc deficiency and zinc supplementation in proliferating tumour tissue, and that the site of action of zinc in this process was probably thymidine kinase, since there was considerable doubt concerning the role of DNA polymerase in DNA synthesis.
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PMID:A site of action for zinc in neoplastic tissue. 17 58

Deoxythymidine kinases (EC 2.7.1.--) induced in HeLa TK- cells by Herpes simplex Type I and Type II viruses both had a requirement for divalent cations. The enzymes had the highest activities in the presence of Mg2+, followed by Mn2+, Ca2+, Fe2+, and in that order, whereas they were inactive in the presence of Zn2+ and Cu2+. The amount of Mg2+ required for optimal activity was dependent on the amount of ATP present, so that optimal activities were found when the concentration of Mg2+ was equal to that of ATP; an excess of Mg2+ inhibited the reaction. The activities of various nucleoside triphosphates as phosphate donors for Herpes simplex virus Type I deoxythymidine kinase were in the order: ATP = dATP = ara ATP greater than CTP greater than dCTP greater than UTP greater than dUTP greater than GTP greater than dGTP. Those for Herpes simplex virus Type II deoxythymidine kinase were in the order: CTP greater than dCTP = ara CTP greater than dATP greater than ATP greater than UTP greater than GTP greater than dUTP = dGTP. For both deoxythymidine kinases induced by Herpes simplex virus, the nucleoside triphosphates tested exerted cooperative effects. The Km values of ATP and CTP for the Herpes simplex virus Type I enzyme were 30 and 70 muM respectively; whereas those for the Herpes simplex virus Typr II enzyme were 140 and 450 muM. Studies on binding of various thymidine analogs with free 5'-OH to these deoxythymidine kinases indicated that 5-substituted ethyl-, vinyl-, allyl-, propyl-, iodo- and bromo-dUrd as well as iodo5 dCyd and bromo5 dCyd had good affinity to both enzymes. In contrast, vinyl5 Urd, iodo5 Urd and arabinosylthymidine had good affinity only to the Herpes simplex virus Type I enzyme but not to the Herpes simplex virus Type II deoxythymidine kinase. All of these thymidine analogs were competitive inhibitors, with KI values in the range of 0.25 to 1.5 muM. Herpes simplex virus Type I deoxythymidine kinase was less sensitive to either dTTP or iodo dUTP inhibition than Herpes simplex virus Type II. Both dThd and dCyd could serve as substrates and competed with each other for Herpes simplex viruses Type I and Type II induced kinases, but they differed in their Km values for these enzymes. The Km values of dThd and dCyd were 0.59 muM and 25 muM for Herpes simplex virus Type I deoxythymidine kinase; while they were 0.36 muM and 88 muM respectively for the Herpes simplex virus Type II enzyme.
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PMID:Deoxythymidine kinase induced in the HELA TK- cells by herpes simplex virus type I and type II. Substrate specificity and kinetic behavior. 18 65

Cadmium administered shortly before or after partial hepatectomy blocks in a dose-dependent manner the increase of thymidine and thymidylate kinase activities in regenerating rat livers. The effect of cadmium can be partially antagonized by simultaneous zinc administration. The intraperitoneal injection of cadmium is more effective than its subcutaneous administration. While there are in vitro differences in the sensitivity of thymidine kinase and thymidylate kinase towards Cd2+-, Zn2%- and Cu2+-ions, both enzymes are equally depressed following their in vivo administration. Cadmium displays the highest inhibitory activity and resembles in this respect beryllium [1].
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PMID:Metabolic alterations of liver regeneration. XV. Cadmium-mediated depression of thymidine and thymidylate kinase induction in rats. 22 69

The activity of deoxythymidine kinase was assayed in implanted sponge connective tissue in three groups of subjects: 1) five normal controls (having normal levels of plasma and red cell zinc); 2) four patients with sickle cell anemia who had low zinc in red cells and hair; and 3) two volunteers (under strict dietary controls), after 6 mo of zinc restriction (2.7 mg/day) and repeated after 3 mo of zinc repletion (30 mg/day). Total protein, total collagen, RNA/DNA, and deoxythymidine kinase activity were measured by techniques reported previously. In sickle cell anemia patients, deoxythymidine kinase activity was not detected, and RNA/DNA, total collagen, and total protein contents were decreased compared to normal controls (statistically significant). In human volunteers deoxythymidine kinase activity was not detected during the zinc restriction phase. After supplementation with zinc, deoxythymidine kinase activity became 70% of normal control levels, and RNA/DNA, total collagen, and total protein contents of sponge connective tissue increased. In conclusion, an adverse effect of zinc deficiency on deoxythymidine kinase activity of implanted sponge connective tissue of man has been demonstrated for the first time.
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PMID:Deoxythymidine kinase activity of human implanted sponge connective tissue in zinc deficiency. 42 58

Accumulation of thymidine kinase activity in vaccinia virus-infected cells was severely inhibited by zinc ions if the drug was added within 1 h postinfection. If added later, zinc ions had no effect on the enzyme synthesis. A fraction of RNA which is normally synthesized in infected cells, was missing from a proper part of the gradient if the cells were treated with zinc ions within 1 h postinfection (as has been shown by cosedimentation of pulse-labeled RNAs in isokinetic gradients). It is suggested that a transcriptional (or posttranscriptional) step is involved in zinc-caused inhibition of vaccinia virus growth.
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PMID:Inhibition of vaccinia virus growth by zinc ions: effects on early RNA and thymidine kinase synthesis. 43 May 99

In rats, of the Wistar-Porton strain, a single intravenous injection of 1.25 mg Cd2+ between days 9 and 15 of gestation results in a high incidence (80% of hydrocephalus, together with other malformations in the fetuses, examined on day 20. This dose is critical, since 1.1 mg Cd2+/kg is not teratogenic, while 1.35 mg Cd2+/kg kills all the embryos. Intravenous injection of Cd2+ to the pregnant rat on day 12 causes a dose-dependent inhibition of placental Zn2+ transport. At the teratogenic dose, Zn2+ transport is inhibited by about 75% at 4 hr. Thereafter, inhibition decreases with time but is still significant at 48 hr. At 20 hr after administration of Cd2+ the embryonic concentration of Zn2+ is depressed by 33%. In the whole embryo the activity of the Zn2+-dependent thymidine kinase is inhibited by about 60% at 4 hr and at 20 hr the DNA concentration is reduced significantly. Placental transport of 14C-leucine and 14C-uridine, as well as the embryonic incorporation of these precursors into protein and RNA is unaffected at least at short times after the administration of Cd2+. It is possible therefore, that the teratogenic effects of Cd2+ may be related to the inhibition of DNA synthesis in the embryo.
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PMID:Acute effects of cadmium on the pregnant rat and embryo-fetal development. 48 38

The effects of a mild zinc-deficient state in humans were studied. Four male volunteers received restricted zinc intake for several weeks under strict metabolic conditions. As a result of dietary zinc restriction, a decrease in zinc concentration of plasma, erythrocytes, leukocytes, and urine was observed. Changes in the activities of zinc-dependent enzymes in the plasma such as alkaline phosphatase and ribonuclease were also related to the dietary zinc status. An adverse effect of zinc restriction on total protein, total collagen, ribonucleic acid, and the activity of deoxythymidine kinase (a zinc-dependent enzyme) in the sponge connective tissue of the two volunteers in whom this test was done was noted. During the zinc restriction period, the ammonia level in the plasma was elevated. Weight loss occurred in all subjects as a result of dietary zinc restriction. Inasmuch as the zinc-deficient state was mild, this study provides a basis for developing diagnostic criteria for zinc deficiency in humans.
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PMID:Experimental zinc deficiency in humans. 69 27

The activity of thymidine kinase in 12-day fetuses taken from females exposed to a dietary zinc deficiency during pregnancy was significantly lower than in ad libitum (P less than .05) and restricted-intake (P less than .01) controls. Activity of the enzyme was not restored by in vitro addition of zinc at levels up to 0.075 mM but severe inhibition (approximately 50%) occurred at 0.75 mM. Enzyme activity was also severely reduced (approximately 44%) by 0.017 mM (0.96 mug/ml) of copper which raises the possibility that the reduction in thymidine kinase accompanying zinc deficiency may arise, at least in part, from an absolute or relative change in the intracellular level of copper.
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PMID:Depressed thymidine kinase activity in zinc-deficient rat embryos. 118 89

To study the relationship between DNA methylation and promoter activity we have methylated in vitro the promoters of the mouse metallothionein I gene and the herpes simplex virus thymidine kinase gene. We have transiently transfected these promoters fused to the human growth hormone in their methylated or unmethylated state into mouse L or F9 cells. Promoters methylated by methylase (M.) Hpa II and M.Hha I caused inhibition of reporter gene expression in L cells but not in F9 cells, while methylation of all CpGs by M.Sss I caused inhibition in both cell lines. Repression of promoter activity by M.Hpa II and M.Hha I methylation, but not by M.Sss I methylation, could be alleviated by cotransfection with an excess of untranscribable DNA methylated with M.Sss I. The methylated sites in nuclei isolated from the transfected L cells, but not F9 cells, were found to be protected from Msp I digestion. Taken together these results suggest that a factor present in L cells and missing in F9 cells mediates the methylation-directed inhibition of promoter activity. The ability of methylated DNA to overcome the inhibition seems to reflect competition for the mediator factor. Interestingly, treatment with Zn2+ ions brought about activation of the methylated promoter of the metallothionein gene. Similarly, butyrate could override the repression of the thymidine kinase methylated promoter. These activations were not accompanied by demethylation of the promoter or displacement of the mediator factor.
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PMID:Inhibition of promoter activity by methylation: possible involvement of protein mediators. 165 Apr 72

Using a transient expression assay in Vero cells, we have shown that the protein product from gene 61 of varicella-zoster virus (VZV) can repress the function of the VZV encoded trans-activators on putative viral immediate-early, early, and late gene promoters. The repression is exerted at the transcriptional level and requires functional gene 61 protein. This trans-repressor is the herpes simplex type 1 ICP0 (a trans-activator) homolog, as defined by gene location, the sharing of a cysteine-rich putative zinc-binding finger in the amino-terminal region, and limited amino acid homology. Open reading frame 61 (ORF61)-mediated trans-repression appears to be specific for VZV-encoded trans-activators in that it has no effect on simian virus 40 and Rous sarcoma virus promoters. Moreover, it does not inhibit trans-activation of the human T-lymphotropic virus type I and human immunodeficiency virus long terminal repeats by tax and tat genes, respectively. We constructed plasmids with mutations in ORF61 and tested them for their ability to inhibit trans-activator (VZV genes 4 and 62)-mediated activation of the viral thymidine kinase promoter-chloramphenicol acetyltransferase construct. Mutants containing interruptions in ORF61 lost their trans-repressing ability, as demonstrated at both the protein and steady-state RNA levels. These results suggest that the ORF61 protein product can mediate down-regulation of VZV gene expression.
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PMID:Characterization of a potent varicella-zoster virus-encoded trans-repressor. 165 42


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