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)

Superinfection of Raji cells with Epstein-Barr virus induced a new thymidine kinase that was distinguishable from both adult and fetal kinases of the host cell by discontinuous electrophoresis on polyacrylamide gels and glycerol gradients.
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PMID:Epstein-Barr virus-associated thymidine kinase. 20 28

A mutant human lymphoblastoid cell line, Raji-TG, resistant to 10micron g 6-thioguanine (TG)/ml was produced from wild-type cells after exposure to ethylmethane sulfonate. The Raji-TG cells showed their failure to incorporate 3H-hypoxanthine, only 2% as much hypoxanthine guanine phosphoribosyl transferase (HPRT) activity as wild-type cells, and no revertant in HAT selective medium containing bypoxanthine, aminopterin, and thymidine. Raji-TG cells, which were maintained routinely in regular medium lacking TG for as long as 2 years, still retained resistance to the drug and inability to grow in HAT medium. A fusion of Raji-TG cells and mouse cells resistant to 5-bromodeoxyuridine and lacking thymidine kinase formed hybrids, and the resulting hybrid colonies proliferated in HAT medium. These observations strongly supported the hypothesis that Raji-TG line cells might be originated from a mutational event with deficiency of HPRT. Both parental and the mutant have a modal chromosome number of 49 with a remarkably stable karyotype. Excess chromosome materials are found in chromosomes 1, 5, 7, 14, and 16. Chromosome 8 is completely missing, but is represented by two respective isochromosomes of the short and long arms of No. 8. Five different marker chromosomes could be distinguished, and most of their origin has been determined. Isolation of Raji-TG X mouse hybrid clones which contained one of each marker chromosome is of considerable value in mapping human genes on regions within particular chromosomes.
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PMID:Karyological characterization of a human lymphoblastoid cell line resistant to 6-thioguanine. 84 67

A clone of the Epstein-Barr virus (EBV) thymidine kinase (TK) gene was derived from a cDNA library of P3HR1 cells. The gene product was expressed as a fusion protein in a procaryotic system by using T7 RNA polymerase. The recombinant TK showed a molecular mass of 67 kDa and was biologically active. Antiserum raised in mice immunized with partially purified TK recognized an antigen present in EBV-superinfected Raji cells using an indirect immunofluorescence assay.
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PMID:Cloning and expression of a cDNA encoding the Epstein-Barr virus thymidine kinase gene. 133 Nov 57

To determine the effect of different promoters on the expression of an altered dihydrofolate reductase (DHFR) gene conferring methotrexate (MTX) resistance in different cell types, double-copy retroviral vectors were constructed carrying a murine mutant DHFR under the control of five different promoters, i.e., human adenosine deaminase (ADA), simian virus 40 (SV40), thymidine kinase (TK), human beta-actin, and cytomegalovirus (CMV). Their expression was compared in NIH-3T3 cells, three human leukemia cell lines, and mouse bone marrow. The variant DHFR is readily expressed from these various promoters in retroviral vectors at a selectable level. In 3T3 cells, the DHFR constructs containing the SV40 promoter conferred the highest levels of resistance to MTX. In K562 and Raji cells, the construct with the TK promoter produced the highest level of resistance. However granulocyte-macrophage colony-forming unit (CFU-GM) colonies from mouse marrow were more resistant to MTX when infected with vectors containing the SV40 promoter and ADA promoter as compared to the other promoter constructs. These studies show that mouse fibroblast cell lines such as NIH-3T3 do not predict the effectiveness of retroviral-mediated gene transfer for marrow progenitor cells, and that the activity of retroviral vector-encoded promoters vary in an unpredictable manner from cell type to cell type. Possible implications for basic gene transfer studies and clinical applications are discussed.
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PMID:Comparison of the expression of a mutant dihydrofolate reductase under control of different internal promoters in retroviral vectors. 152 11

We have studied the relative rate of transcription across the Epstein-Barr virus genome in the Burkitt's lymphoma cell line Raji by nuclear run-on analysis during latency and after induction of an abortive lytic cycle with 12-0-tetradecanoylphorbol 13-acetate (TPA) and 5-iodo-2'-deoxyuridine (IUdR). During latency the entire, or almost the entire, viral genome was found to be transcriptionally active to a low or intermediate extent, with some variation in activity along the genome. The fragment with the highest transcriptional activity was EcoRI J, which contains the genes encoding the small nuclear RNAs EBER1 and -2, transcribed predominantly by RNA polymerase III. An intermediate level of transcription was observed between positions 10 and 138 (kb), with areas of slightly higher activity on the large internal repeats and the left duplicated region (DL). The remaining part of the viral genome, between position 138 and the termini, and the termini and position 10 (kb) (with the exception of the EcoRI J fragment), showed very little transcriptional activity, except for the intermediately active regions carrying the righthand oriLyt (DR) and the terminal repeats. Upon induction of the viral genome with TPA and IUdR, the viral genome was transcriptionally active at a rate at least tenfold that seen during latency. Polymerases were not equally distributed along the genome after induction; the highest density was found in regions 48 to 58 kb, 82 to 84 kb, 102 to 104 kb, 118 to 122 kb and 142 to 145 kb of the viral genome. High transcriptional activity correlated with distinct transcription units in some cases, i.e. BamHI H1LF1 (DL), BamHI MLF1, BamHI ZLF1/BamHI RLF1 and BamHI X (thymidine kinase), but not in others (BamHI H2). Besides initiation of transcription, other regulatory processes such as stabilization and processing of primary transcripts may also contribute to regulation of virus gene expression. Addition of cycloheximide completely abolished the transcriptional activation of the genome mediated by TPA and IUdR.
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PMID:Transcriptional activity across the Epstein-Barr virus genome in Raji cells during latency and after induction of an abortive lytic cycle. 165 54

The loss of expression of the enzyme O6-methylguanine-DNA methyltransferase (the Mex- phenotype), which often results from cellular transformation, confers hypersensitivity to alkylating agents. We have observed two unrelated examples in which human cell lines have undergone a spontaneous alteration in their Mex phenotype during propagation in vitro. The change was reversible and was not the result of mutation. In both cases a loss of methyltransferase expression was accompanied by a simultaneous loss of expression of two metabolically unrelated enzymes: thymidine kinase and galactokinase. "Reversion" to methyltransferase expression was accompanied by simultaneous reexpression of both kinase activities. A third example of this coordinate gene regulation was seen with the Burkitt's lymphoma cell line Raji which expresses methyltransferase, thymidine kinase, and galactokinase at high levels. A thymidine kinase- Raji cell line derived by bromodeoxyuridine mutagenesis that is also Mex- was found to be galactokinase-. It appears that methyltransferase expression may in some instances be coordinately regulated with the tk and glk loci which are closely linked on human chromosome 17.
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PMID:Coregulation of the human O6-methylguanine-DNA methyltransferase with two unrelated genes that are closely linked. 213 69

We have investigated the expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase in the Burkitt's lymphoma cell line Raji. An existing mutant Raji cell line which lacks thymidine kinase activity had previously been shown to be Mex- and to no longer express O6-methylguanine-DNA methyltransferase. We report here that in addition to the methyltransferase and thymidine kinase, a third enzyme with an unrelated function, galactokinase, is also not expressed in Raji cells. The control of thymidine kinase expression is post-transcriptional and it is possible that galactokinase and methyltransferase can share a common post-transcriptional regulation with thymidine kinase.
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PMID:Regulation of O6-methylguanine-DNA methyltransferase expression in the Burkitt's lymphoma cell line Raji. 223 4

Epstein-Barr virus (EBV) has long been implicated in nasopharyngeal carcinoma (NPC). Recent studies in our and other laboratories have shown a correlation between the disease and high antibody titers to EBV-specific DNase. These data led us to also examine serial sera from healthy adults and patients with infectious mononucleosis or NPC, for their capacity to neutralize the EBV-specific thymidine kinase (TK) activity from chemically induced EBV-carrying human lymphoblastoid cells. Our results were the following: (i) sera were found that efficiently blocked the EBV-specific TK activity of induced-Raji TK- cell extracts, but not the host-cell TK activity from EBV-negative BJAB cells; (ii) a relationship appeared between high levels of EBV-specific TK-neutralizing activity in sera and NPC pathology, even though in this preliminary study the degrees of EBV-induced TK-blocking activity detected in sera were not significantly correlated with EBV-specific antibody titers; (iii) the EBV-induced TK-neutralizing activity was found in the main IgG fraction derived from NPC sera. These data must be compared with other known antibody responses to EBV for their clinical interest in NPC control.
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PMID:Relationship between nasopharyngeal carcinoma and high antibody titers to Epstein-Barr virus-specific thymidine kinase. 253 7

3'-Azido-2',3'-dideoxythymidine (AZT) and 2',3'-didehydro-2',3'-dideoxythymidine (D4T) are potent and selective inhibitors of human immunodeficiency virus replication in MT-4 and ATH8 cells. They are also inhibitory to the replication of murine retroviruses, i.e. Moloney murine sarcoma virus-induced transformation of C3H cells. In MT-4 cells AZT is readily phosphorylated to its 5'-monophosphate, while the 5'-di- and 5'-triphosphates are generated to a 200-600-fold lower extent than the 5'-monophosphate. D4T is phosphorylated in MT-4 cells to its 5'-monophosphate at a 300-600-fold lower extent than AZT. The phosphorylation of AZT in the thymidine kinase-deficient cell line (Raji/TK-) is severely depressed, while D4T phosphorylation is only slightly diminished in Raji/TK- as compared to Raji/0 cells. D4T has a 10-fold lower affinity for phosphorylation by crude MT-4 cell extracts than AZT (Km, 142 and 14 microM, respectively), and the Vmax for phosphorylation of D4T is only 5% that of AZT. D4T is phosphorylated by MT-4 cell extracts about 180-fold less efficiently than AZT (Vmax/Km, 0.06 for D4T, as compared to 11 for AZT), and this is consistent with the differences found in the amounts of phosphorylated products of D4T and AZT formed in intact MT-4 cells. The 5'-triphosphates of AZT and D4T are equipotent in their inhibitory effects on the reverse transcriptases from human immunodeficiency virus and Moloney murine leukemia virus.
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PMID:Differential patterns of intracellular metabolism of 2',3'-didehydro-2',3'-dideoxythymidine and 3'-azido-2',3'-dideoxythymidine, two potent anti-human immunodeficiency virus compounds. 253 71

Epstein-Barr (EB) virus induces a new pyrimidine deoxynucleoside kinase [thymidine kinase (dTk)] activity in Raji B lymphocyte cells after superinfection. This dTk activity is also present in small amounts in the HR-1 virus-producer cell line and in larger amounts in the B95-8 virus-producer line. The dTk activity induced by EB virus coelutes from DEAE-cellulose columns with deoxycytidine kinase (dCk) activity and elutes as a broad peak well separated from the large peaks of cellular dTk and dCk activities. This EB virus-induced pyrimidine deoxynucleoside kinase activity from HR-1 cells differs from cellular kinases in most basic biochemical properties but shares certain properties with the herpes simplex virus dTk.
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PMID:Epstein-Barr virus induces a unique pyrimidine deoxynucleoside kinase activity in superinfected and virus-producer B cell lines. 299 May 49


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