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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The current state of knowledge concerning the biochemical transformation by Herpes Simplex virus (HSV) of mammalian cells lacking the enzyme thymidine kinase (TK) is reviewed. Transformation of thymidine kinase negative mouse cells (LTK-) to the TK+ phenotype by ultraviolet light-inactivated HSV preparations depends both on the irradiation dose and on the multiplicity of infection. Once stably associated with the transformed cell, the HSV thymidine kinase appears to be regulated differently than the cellular enzyme: HSV TK activity is maximal in stationary cells, whereas cellular TK activity is maximal during the S-pphase of growing cells. Furthermore, infection with an HSV TK- mutant virus leads to the induction of TK activity in HSV TK+ cells, but not in normal TK+ cells. Recent studies indicate that in addition to the TK gene, at least one other HSV gene, perhaps a structural antigen of the virion, is also transferred to TK- cells. This is consistent with the finding that a clone of HSV TK+ cells harbors approximately five copies per cell of 23 per cent of the HSV genome.
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PMID:Thymidine kinase gene transfer by herpes simplex virus. 18 68

LTK-cells infected with UV-irradiated HSV produce transformants that contain a thymidine kinase (TK) activity not found in the parental LTK-line (Munyon et al., 1971). One of these (TK+) transformants (clone 139) has been analysed for the presence of the HSV genome. Reassociation kinetics studies with iodinated HSV DNA of specific activity of about 9 x 107 cpm/mug have established that there are approximately six copies of a fragment comprising about 15% of the HSV genome in HSV-transformed clone 139. Neither the parental LTK-nor a "revertant" cell line (clone 139 BUDR) obtained from clone 139 showed any detectable HSV-specific sequences. Analysis of data on RNA-125I-HSV DNA reassociation kinetics indicates that perhaps 5% of the HSV genome is transcribed in HSV-transformed clone 139. These results indicate that transformation is probably maintained by the presence of only a fraction of the HSV genome in the TK+ clones.
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PMID:Presence of a herpes simplex virus type 1 genome fragment in HSV-transformed cells. 19 Jan 47

Herpes simplex virus type 1 (HSV-1) infection induces expression of the human immunodeficiency virus type 1 (HIV-1) provirus in the chronically infected T-cell line ACH-2. The HSV-1-mediated induction correlates with the appearance of two NF-kappa B-specific proteins of 55 and 85 kDa in the nucleus and with the binding of 50-kDa nuclear protein to the LBP-1 binding site of the untranslated leader sequence of the HIV-1 long terminal repeat. The HSV-1-induced LBP-1 binding protein, designated HLP-1, is present exclusively in HSV-1-infected, but not in phorbol-12-myristate-13-acetate- or tumor necrosis factor alpha-treated ACH-2 cells. Both the NF-kappa B and LBP-1 target sequences, when inserted either alone or together 5' of a heterologous minimal promoter (thymidine kinase), confer inducibility by HSV-1 infection in a transient transfection assay. Thus, it appears that the HSV-1-mediated activation of HIV-1 provirus is brought about by the binding of both NF-kappa B and HLP-1 specific proteins to two distinct regions of HIV-1 long terminal repeat.
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PMID:Herpes simplex virus type 1-mediated induction of human immunodeficiency virus type 1 provirus correlates with binding of nuclear proteins to the NF-kappa B enhancer and leader sequence. 131 71

The epidermal growth factor (EGF) receptor (EGFR) promoter is negatively regulated by thyroid hormone and retinoic acid. This regulation can be mapped to a 36-basepair GC-rich region of the promoter (EGFR P/E) that functions autonomously as a promoter and an enhancer when placed in front of the thymidine kinase gene TATA element. Direct high affinity binding of the thyroid hormone receptor (T3R) to this element requires a nuclear protein. Through ion exchange chromatography and gel filtration of HeLa nuclear extract, this activity was identified as a protein of approximately 67 kilodaltons. This protein did not bind to DNA alone, but greatly augmented T3R binding to the EGFR P/E sequence in gel mobility shift and DNA precipitation assays. When combined with the T3R auxillary protein (TRAP), the T3R migrated as a larger complex on the DNA. Chemical cross-linking identified this complex as a heterodimer between T3R and TRAP. T3R-TRAP binds to a 7-basepair site in the EGFR P/E (GGGACTC) that has weak homology to a consensus thyroid response element half-site. Thus, on this element, T3R-TRAP heterodimers contact the DNA primarily on a single site that comprises an inhibitory thyroid response element.
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PMID:A nuclear protein is required for thyroid hormone receptor binding to an inhibitory half-site in the epidermal growth factor receptor promoter. 158 25

Previous studies have shown that at least three polypeptides of 43, 39 and 38 kDa are translated from separate AUG codons of the thymidine kinase (TK) encoding mRNA of herpes simplex virus type 1. In addition, small tk-specific transcripts initiated within the tk coding region were observed. However, functional activity of these three proteins and their role in establishing of the TK+ cell phenotype is not yet clear. In order to locate the 5' boundary of the gene encoding functionally active TK, we constructed a set of deletion mutants with truncated 5' ends and examined their ability to provide a TK+ phenotype after microinjection into nuclei of LTK- cells. The results demonstrate that nucleotide sequences upstream from the second ATG codon can be removed without affecting the TK+ phenotype. Deletion of the second start codon and its downstream region inactivates the TK function. Those deletion mutants which contain only the third ATG codon are TK-. Thus, the 38-kDa polypeptide that initiates at the third start codon is not endowed with the TK+ activity. Constructs containing deletions up to nt +210 and lacking all 5'-end canonical and aberrant transcription control regions, as well as first start codon, can provide the TK+ function.
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PMID:Transient expression of deletion mutants of the herpes simplex virus thymidine kinase-encoding gene in mouse fibroblast cells. 165 25

The transcriptional induction of the alpha or immediate-early gene class of herpes simplex virus type 1 effected by the alpha trans-induction factor (alpha TIF, ICP25, VP16, Vmw65) requires an alpha-specific cis-acting site. Increased transcription does not result from the direct, independent binding of alpha TIF, but rather from an alpha TIF-dependent formation of a protein-DNA complex containing, in addition to alpha TIF, at least one host cell factor. One of the host factors is a POU domain protein which recognizes an octamer element in the alpha-specific consensus. There is evidence that alpha TIF may drive the formation of multiple protein-DNA complexes containing a POU protein and additional host factors. Previously, the gene products of UL46 and UL47 have been implicated in modulating the alpha TIF-dependent transcriptional induction of alpha genes. Our current studies have extended these analyses from a transient-expression system to a series of viral deletion mutants. In these studies we demonstrate that neither UL46- nor UL47-encoded gene product, either separately or in combination, is required for viral growth in cell culture. The absence of UL47 reduces by up to 80% the ability of the virus to induce an alpha-regulated thymidine kinase reporter gene resident in 143TK- cells. Autoradiograms of [35S]methionine pulse-labeled infected cell proteins, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, show that deleting UL46 and/or UL47 has no discernable effect on the synthesis of alpha TIF or alpha TIF-containing proteins. Subsequent Western immunoblot analysis, with rabbit anti-alpha TIF antibodies made to an alpha TIF-Staphylococcus aureus protein A fusion, demonstrated that the accumulation and steady-state levels of alpha TIF or alpha TIF-containing proteins was indistinguishable from that of the thymidine kinase-negative isogenic parental virus, R delta 305.
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PMID:Role of herpes simplex virus type 1 UL46 and UL47 in alpha TIF-mediated transcriptional induction: characterization of three viral deletion mutants. 184 1

Aside of the gene coding for cytoplasmic thymidine kinase, the genome of mouse cells carries two pseudogenes. Both are inactive in situ. One of the pseudogenes is a processed pseudogene in which a two base pair deletion caused a shift of the reading frame and a shortening of the gene product from the 233 amino acids of thymidine kinase to 177 amino acids in the pseudogene product. We report here that introduction of this pseudogene into LTK- cells gave rise to cells with a thymidine kinase positive phenotype. The transformed cells carried multiple copies of the pseudogene the upstream region of which exhibited low but measurable promoter activity. Replacement of the upstream region of the pseudogene by a promoter of Simian virus 40 or of the mammary tumor virus resulted in high transfection efficiencies and in cell lines exhibiting high thymidine kinase activities.
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PMID:The processed pseudogene of mouse thymidine kinase is active after transfection. 217 83

To study the influence of clustered highly repetitive DNA sequences on the expression of adjacent genes, LTK- cells were cotransfected with the herpes simplex virus thymidine kinase (tk) gene and mouse satellite DNA. TK+ transformants containing a few copies of the tk genes flanked by satellite DNA were isolated. In situ hybridization on the metaphase chromosomes indicated that in each cell line the TK sequences resided at a single chromosomal site and that integration occurred preferentially into regions of the cellular DNA rich in highly repetitive sequences. The prominent feature of these cell lines was their phenotypic instability. Suppression and reexpression of the tk gene occurred at high frequency (greater than 3%) and did not correlate with any significant change in the organization of foreign DNA or with the presence of selective agents. These results indicate that satellite DNA, the major component of constitutive heterochromatin, may influence the expression of adjacent genes by affecting the chromatin structure.
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PMID:Satellite DNA induces unstable expression of the adjacent herpes simplex virus tk gene cotransfected in mouse cells. 283 71

Thyroid hormone dependent transcription stimulatory and inhibitory elements exist at the 5'-end of the rat GH (rGH) gene (TSE and TIE, respectively). In this study, the location of the sequences essential for TSE activity was examined using stably transfected GC cells. Because the TIE may influence TSE activity, we investigated TSE activity both on the rGH promoter, in the presence of the TIE, and on the viral thymidine kinase promoter, with the TIE deleted. The results of these studies indicate that the minimum sequences essential for TSE activity exist between positions -194 and -169 of the rGH gene.
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PMID:Sequences essential for activity of the thyroid hormone responsive transcription stimulatory element of the rat growth hormone gene. 284 60

Recombination between a 360-base-pair (bp) segment of a wild-type thymidine kinase gene (tk) from each of three different strains (F, MP, and 101) of herpes simplex virus type one and a complete herpes simplex virus type 1 (strain F) tk gene containing an 8-bp insertion mutation was studied. The pairs of tk sequences resided as closely linked repeats within the genome of mouse LTK- cells. The frequency of recombination between sequences exhibiting 232 bp of uninterrupted homology and containing no mismatches other than the insertion mutation was comparable to the frequency of recombination between two sequences exhibiting four additional nucleotide mismatches distributed in such a way to preserve the 232-bp stretch of contiguous homology. In contrast, the placement of only two single-nucleotide mismatches (in addition to the insertion mutation) in such a manner to reduce the longest uninterrupted homology to 134 bp resulted in a 20-fold reduction in recombination. We conclude that the rate of intrachromosomal recombination in mammalian cells is determined by the amount of uninterrupted homology available and not by the total number of mismatches within a given interval of DNA. Furthermore, efficient recombination appears to require between 134 and 232 bp of uninterrupted homology; single-nucleotide heterologies are most likely sufficient to disrupt the minimal efficient recombination target. We also observed that if recombination was allowed to initiate within sequences exhibiting perfect homology, the event could propagate through and terminate within adjacent sequences exhibiting 19% base pair mismatch. We interpret this to mean that heterology exerts most of its impact on early rather than late steps of intrachromosomal recombination in mammalian cells.
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PMID:Dependence of intrachromosomal recombination in mammalian cells on uninterrupted homology. 285 96


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