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)

Transcription of the complete mouse mammary tumor virus (MMTV) proviral genome in mouse cells is controlled by a strong promoter in its long terminal repeat. In the mouse T lymphoma EL4, there is a second, activation-dependent transcriptional initiation site within the envelope (env) gene, from which a short mRNA is generated, encoding the open reading frame of the long terminal repeat. We now report the isolation of a segment of the MMTV env gene (called META, for MMTV env transcriptional activator) which has the expected transcription-activating properties seen in EL4.E1 cells. Namely, it induces activation-dependent, T-lymphocyte-specific transcription of a chloramphenicol acetyltransferase reporter gene. It is active in mouse or human T-helper lymphocyte lines when they are stimulated to transcribe lymphokine genes but is inactive in unstimulated T-helper cells, fibroblasts, a cytotoxic T-lymphocyte line, and a mastocytoma cell line. Its activity is inhibited by cyclosporin A, a specific inhibitor of lymphokine transcription. Several forms of the META have been isolated from EL4.E1 cells, a mouse T-helper cell hybridoma, and from BALB/c spleen cells. Linked to the heterologous thymidine kinase promoter, a 400-bp portion of it is an inducible, orientation-independent, and cyclosporin A-sensitive transcriptional activator in T-helper cells.
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PMID:An activation-dependent, T-lymphocyte-specific transcriptional activator in the mouse mammary tumor virus env gene. 132 Jan 98

Benzanthracene-induced C57BL/6 (H-2b) mouse T-cell lymphoma EL4 (a thymidine kinase-deficient cell line) was fused by using polyethylene glycol with an Mlsa (Mls for minor lymphocyte stimulatory) antigen-dependent T cell line, which was designated G4 and had been derived from a C3H/He mouse (H-2k), and the fused cells were cultured in HAT medium. Although no growing cells appeared in most of these fusions, we consistently obtained growth-arrested H-2Kb-positive cells from the fused cell populations by the panning method. The cells were tetraploid and were able to proliferate in response to Mlsa antigen. Three H-2Kb-positive clones, isolated by limiting dilution from three different fusions, were shown to be EL4 x G4 hybrids, because (1) they had both H-2k and H-2b antigens; (2) each of the clones had one submetacentric chromosome which was a marker chromosome of EL4, and they were tetraploid with modal chromosome numbers of 74, 78, and 79, respectively; (3) they had 4 isozymes of both parental cells. These results indicate that EL4 lymphoma cells cease to proliferate when fused with T cell line G4. The malignant phenotype of lymphoma EL4 is thus suppressed at the level of cell transformation by the introduction of the G4 cell genome.
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PMID:Cessation of autonomous proliferation of mouse lymphoma EL4 by fusion with a T cell line. 230 41

Granulocyte-macrophage (GM)-CSF and IL-3 are hemopoietic growth factors whose genes are closely linked in both humans and mice. In humans, the GM-CSF and IL-3 genes are regulated by a cyclosporin A-inhibitable enhancer located 3 kb upstream of the GM-CSF gene that is inducible by signals that mimic TCR activation. To search for a murine homologue of this enhancer we probed mouse genomic DNA and located a 400-bp element 2 kb upstream of the mouse GM-CSF gene that was 76% homologous with the human GM-CSF enhancer. Like the human GM-CSF enhancer, this element formed a cyclosporin A-inhibitable DNase I-hypersensitive site in the murine T cell line EL4 upon activation with phorbol ester and calcium ionophore. Transient transfection assays showed that this homologue of the human enhancer acted as an inducible enhancer of the thymidine kinase promoter, the mouse IL-3 promoter, and the human GM-CSF promoter. We observed, however, that the mouse GM-CSF promoter was significantly more active than the human GM-CSF promoter and found that it supported a level of activity equivalent to the combination of the human GM-CSF promoter and the human GM-CSF enhancer. Consequently, the activity of mouse GM-CSF promoter was not significantly elevated in the presence of the mouse GM-CSF enhancer. Because the mouse GM-CSF enhancer is considerably less active than its human homologue we suggest that the mouse GM-CSF gene has evolved with less dependence upon the upstream enhancer for its activation.
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PMID:Transcriptional regulation of mouse granulocyte-macrophage colony-stimulating factor/IL-3 locus. 760 99