Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dibutyryl cyclic AMP inhibits the increase of dThd and BrdUrd transport normally observed after infection with Herpesvirus hominis, type I and II. Incorporation is also reduced. Inhibition of uptake is non-competitive as analysed by the Lineweaver-Burk plot. Addition of this drug to infected cells also reduces the activity of the thymidine kinase (EC 2.7.1.75). Transport of dUrd, dCyd and dAdo is not reduced. 4--8 h after infection with thymidine kinase (+) herpes strains the level of cAMP increases. On infection with a thymidine kinase (-) virus, only a small elevation of cAMP can be shown. It was also found that early addition of actinomycin D or of cycloheximide prevents the increase of the cAMP level. This increase seems to depend on the activity of the herpes genome, because ultraviolet irradiation of infective particles destroys this ability.
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PMID:Influence of dibutyryl cyclic AMP on thymidine uptake by herpes simplex virus infected cells and the intracellular level of cyclic AMP. 19 14

The interaction of promoters contained in a Moloney murine leukemia virus (MoMLV)-based retroviral vector was studied after infection of FTO-2B rat hepatoma and NIH 3T3 mouse fibroblast cells. Segments of the phosphoenolpyruvate carboxykinase (PEPCK) promoter-regulatory region, which are known from previous studies to confer responsiveness to hormones, were linked to the structural genes for bovine growth hormone, amino-3'-glycosyl phosphotransferase (neo), and herpes-virus thymidine kinase and inserted into a MoMLV-based retroviral vector. In vectors in which PEPCK was the only internal promoter, it was the major site of gene transcription. This dominant effect was independent of the orientation of the PEPCK promoter relative to the 5' long terminal repeat of the provirus and was noted with as little as -174 base pairs of the 5'-flanking sequence. NIH 3T3 cells, which do not express the endogenous PEPCK gene, transcribed the transduced PEPCK-chimeric genes at the same high levels as was observed in hepatoma cells. When two promoters were present in the provirus, the expression of chimeric structural genes depended on the relative position and orientation of these genes as well as the type of cell infected by the retrovirus. Differential responses of proviral promoters in infected cells were also observed in the presence of hormones. Dibutyryl cyclic AMP increased the expression of genes linked to the PEPCK promoter in FTO-2B and NIH 3T3 cells, whereas glucocorticoids stimulated transcription from both the PEPCK promoter and the long terminal repeat in FTO-2B cells. The effect of these hormones on transcription of proviral promoters depended on their position relative to the 5' long terminal repeat. In contrast, insulin uniformly inhibited transcription from the PEPCK promoter in a position-independent manner but only in hepatoma cells and not in fibroblasts. In clonally isolated FTO-2B cells infected with a retrovirus, the site of proviral integration was also a major factor determining the expression and hormonal regulation from the internal promoters. The data suggest that the hormonal regulation of the expression of genes contained in retroviral vectors depends on the type and position of the regulatory elements present in the provirus and the lineage of the infected cell.
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PMID:Hormonal control of interacting promoters introduced into cells by retroviruses. 202 56

cAMP stimulates the transcription of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) in rat liver. We have investigated the nucleotide sequences required for regulation of PEPCK gene expression by cAMP. A chimeric gene was constructed in which a 620-base pair fragment of the 5'-end of the PEPCK gene (including 547 base pairs of 5'-flanking sequence) was ligated to the herpes simplex virus thymidine kinase (TK) structural gene. The PEPCK promoter fragment was introduced either in the proper orientation for transcription of the TK gene or in the opposite orientation. These fusion genes and the parent vector, pOPF, which contains the intact TK gene, were transfected individually into TK-deficient FTO-2B rat hepatoma cells. FTO-2B cells contain an active endogenous PEPCK gene which is stimulated by cAMP. Cells were selected in HAT medium and grown either as mass cell cultures or as individual clones. Dibutyryl cyclic AMP (Bt2cAMP) plus theophylline (16 h) stimulated TK activity 1.6-6.1-fold in cell lines transfected with the PEPCK-TK fusion gene containing the PEPCK promoter fragment in the correct orientation. However, the intact TK gene was not induced by Bt2cAMP after transfection, nor was there any expression of the PEPCK-TK fusion gene in cells which contained the PEPCK promoter fragment in the wrong transcriptional orientation. Bt2cAMP also increased the levels of TK mRNA in cells transfected with the PEPCK-TK fusion gene, but not in cells transfected with the intact TK gene. The chimeric PEPCK-TK mRNA initiated at the PEPCK start site, as determined by S1 nuclease mapping. There was no relationship between the number of copies of the PEPCK-TK gene integrated in the various cell lines and either the basal level of TK activity or its inducibility of Bt2cAMP.
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PMID:Identification of a cAMP regulatory region in the gene for rat cytosolic phosphoenolpyruvate carboxykinase (GTP). Use of chimeric genes transfected into hepatoma cells. 609 Apr 58