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:2.3.1.28 (chloramphenicol acetyltransferase)
5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the ability of the neu tyrosine kinase to induce a signal for the activation of cell growth-regulated genes. Serum-starved NIH 3T3 cells expressing an epidermal growth factor receptor (EGF-R)/neu construct encoding a hybrid receptor protein were stimulated with EGF and the activation of the neu tyrosine kinase and stimulation of growth factor inducible genes were followed at the mRNA, protein, and activity levels, and compared to the corresponding responses in the neu proto-oncogene and oncogene expressing cells. Induction of the expression of jun mRNAs was an immediate early effect of EGF stimulation, followed by a marked increase in the biosynthesis of the fos/jun transcription factor complex and an increased transcription factor activity as measured by a recombinant transcription unit using chloramphenicol acetyltransferase assays. In distinction, elevated AP-1/PEA-1 activity in the absence of a significant increase in jun and fos expression was characteristic of the neu oncogene-expressing cells. The glucose transporter mRNA increased at 2 h of EGF stimulation and was associated with enhanced glucose transport of the EGF-treated cells. An increase of ornithine decarboxylase (ODC) mRNA and activity followed these changes. In contrast, serum-starved, EGF-treated neu proto-oncogene- and oncogene-expressing cells showed constitutively low and high glucose transporter and ODC activities, respectively. These findings demonstrate that the chimeric EGF-R/neu receptor is capable of activating the expression of both immediate early genes and biochemical activities associated with cell growth stimulation.
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PMID:Activation of the neu tyrosine kinase induces the fos/jun transcription factor complex, the glucose transporter and ornithine decarboxylase. 257 1

Two distinct regions of the transforming growth factor-beta 1 (TGF-beta 1) promoter are responsive to autoregulation and activation by phorbol ester (12-O-tetradecanoylphorbol-13-acetate): sequences located between nucleotides -454 to -323 (first promoter) and between the two transcriptional start sites. We have now characterized in detail the induction of the second promoter (sequences between nucleotides + 1 to +271) of the TGF-beta 1 gene by both TGF-beta 1 and phorbol ester. By assaying progressively deleted mutations in the second promoter, we have found two regions responsible for the induction; each contains a phorbol ester-responsive element. In vitro transcription of the second promoter-chloramphenicol acetyltransferase chimeric genes using nuclear extracts of A-549 cells showed that deletion of the putative phorbol ester-responsive elements results in a 70-80% decrease in activity. DNase I footprinting and gel mobility shift assays showed that binding to an Sp1 site and the putative TRE elements are required for maximal expression of the second promoter region of the TGF-beta 1 gene. These results suggest that AP-1, which is capable of conferring phorbol ester or TGF-beta 1 responsiveness, is the major transcription factor involved in the second promoter-derived transcription of the TGF-beta 1 gene.
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PMID:Activation of the second promoter of the transforming growth factor-beta 1 gene by transforming growth factor-beta 1 and phorbol ester occurs through the same target sequences. 280 30

We have examined the control sequences for the late promoter function of simian virus 40 (SV40) in COS-1 cells which produce SV40 T antigen constitutively. Plasmids were constructed by cloning mutant late promoter segments upstream from sequences coding for the bacterial chloramphenicol acetyltransferase (CAT) gene, and were converted to "double-origin" type by inserting functional replication origin segments downstream from the CAT gene for replicative competence when necessary. The late promoter activity was determined by transient expression assay of the CAT mRNA and enzyme activity levels following DNA-mediated gene transfer into COS-1 cells. We find that the minimal replication origin and the 21-bp repeat containing T antigen and transcription factor Sp1 binding sites, respectively, are dispensable for late promoter function provided that one copy of the 72-bp repeat enhancer is present. We have mapped within the 72-bp repeat the major late promoter component in a 68-bp fragment (located between nucleotides 205 and 272), and found an overlapping 55-bp fragment (located between nucleotides 179 and 234) to have about one-fifth of the late promoter activity. Both the 68- and 55-bp fragments lack some of the core sequence elements required of the 72-bp repeat for transcriptional enhancer activity, and lack the ability to enhance the activity of the SV40 early promoter. The results suggest that the organization of functional units of the 72-bp repeat required for transcriptional enhancement of the early promoter is different from that required for late promoter function. The 21-bp repeat was found to have some late promoter activity located within the origin-distal copy in the absence of the 72-bp repeat. In association with the 21-bp repeat, the otherwise dispensable origin-proximal 22-bp of the 72-bp repeat containing activator protein AP-1 binding site augmented late promoter activity by three- to fourfold.
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PMID:Functional anatomy of the simian virus 40 late promoter. 283 21

The adenovirus early region 3 (E3) promoter is an early viral promoter which is strongly induced by the adenovirus transactivator protein E1A. DNase I footprinting with HeLa cell extracts has identified four factor-binding domains which appear to be involved in basal and E1A-induced transcriptional regulation. These binding domains may bind TATA region-binding factors (site I), the CREB/ATF protein (site II), the AP-1 protein (site III), and nuclear factor I/CTF (site IV). Recently, it has been shown that the DNA-binding domain of transcription factor AP-1 has homology with the yeast transcription factor GCN4 and that the yeast transactivator protein GAL4 is able to stimulate transcription in HeLa cells from promoters containing GAL4-binding sites. These results suggest an evolutionary conservation of both transcription factors and the mechanisms responsible for transcriptional activation in Saccharomyces cerevisiae and higher eucaryotic organisms. To determine whether similar patterns of transcriptional regulation were seen with the E3 promoter in HeLa and yeast cells, the E3 promoter fused to the chloramphenicol acetyltransferase (cat) gene was cloned into a high-copy-number plasmid and stably introduced into yeast cells. S1 analysis revealed that similar E3 promoter mRNA start sites were found in yeast and HeLa cells. DNase I footprinting with partially purified yeast extracts revealed that four regions of the E3 promoter were protected. Several of these regions were similar to binding sites determined by using HeLa cell extracts. Oligonucleotide mutagenesis of these binding domains indicated their importance in the transcriptional regulation of the E3 promoter in yeast cells. These results suggest that similar cellular transcription factor-binding sites may be involved in the regulation of promoters in both yeast and mammalian cells.
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PMID:Adenovirus transcriptional regulatory regions are conserved in mammalian cells and Saccharomyces cerevisiae. 297 53

The neuropeptide substance P (SP) is one of the principal mediators of neurogenic inflammation as well as a neurotransmitter in nociceptive affect neurons. The mechanisms by which binding of SP to its receptor stimulates diverse downstream biologic effects remain unknown. In order to elucidate this process we have established stably transfected cell lines expressing functional rat SP receptors (KNRK-SPR). When stimulated by SP, KNRK-SPR cells respond by simultaneously mobilizing intracellular Ca2+ and increasing cAMP levels. To determine if SP stimulation activates downstream transcriptional regulatory factors, we transfected KNRK-SPR cells with plasmids containing the activator protein 1 (AP-1) and cAMP-responsive (CRE) enhancer elements coupled to the chloramphenicol acetyltransferase (CAT) reporter gene. Stimulation with SP 1-1,000 nM caused a 1.5- to 2-fold increase in CAT activity in both AP-1-CAT- and CRE-CAT-transfected KNRK-SPR cells. Northern and Western blot analyses demonstrate that the mechanism by which SP stimulates AP-1 enhancer activity involves increases in both c-jun mRNA and protein. Moreover, gel retardation assays with oligomers containing the AP-1 and CRE binding sites showed that SP induces specific retardation bands consistent with increases in AP-1 and CRE complexes. These experiments suggest that SP-mediated stimulation of cells involves the participation of two signaling pathways resulting in several transcriptional regulatory mechanisms being activated.
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PMID:Stimulation of transcriptional regulatory activity by substance P. 748 29

We have investigated the differential effects of ultraviolet light(UV) and ionizing radiation (IR) on human immunodeficiency virus type 1 (HIV) and c-jun expression in HIVcat/HeLa cells. This cell line harbors integrated copies of the chloramphenicol acetyltransferase (cat) gene under control of the HIV promoter. Both UV and IR increased the binding of nuclear proteins to an oligonucleotide spanning the HIV enhancer region nuclear factor kappa B sites, but only UV increased HIVcat steady-state mRNA and CAT activity. By comparison, transcription of the cellular c-jun gene increased after both types of radiation, but UV was at least 5-fold more effective than IR despite the fact that protein binding to an activator protein 1 oligonucleotide increased similarly after both UV and IR. The lack of HIVcat transcriptional response after IR does not appear to be the result of the repressor binding to upstream promoter elements since cells stably transfected with different HIV promoter deletions showed a lack of response to IR distinguishable from that of the intact promoter. While our findings indicate no correlation between increased binding of transcription factors to upstream promoter elements and increased expression of these genes after radiation, we did observe major differences in how UV and IR affected chromatin structure. UV produced extensive global chromatin decondensation, whereas IR did not, as seen in the microscope and determined by the increased susceptibility of chromatin to micrococcal nuclease digestion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ionizing radiation activates nuclear factor kappa B but fails to produce an increase in human immunodeficiency virus gene expression in stably transfected human cells. 749 8

In differentiated 3T3-F442A adipocytes, insulin stimulated rapid and transient phosphorylation of c-Jun. Insulin also stimulated phosphorylation of c-Fos and several Fos-related proteins (pp72, pp45, and pp39) as indicated by precipitation with anti-c-Fos antibody following exposure to denaturating conditions. Phosphorylation of c-Fos was stimulated by 7-fold by 60 min, while phosphorylation of Fos-related proteins reached maxima of 3.5-5.5-fold at 15 to 60 min. The increase in phosphorylated c-Fos was due to an increase in both c-Fos protein and the stoichiometry of c-Fos phosphorylation, and was not observed in c-fos (-/-) cells. Additionally, insulin stimulated phosphorylation of a protein with molecular mass of approximately 82 kDa on tyrosine residues by 2.5-fold within 30 min; this protein appeared to be immunologically related to c-Fos. These increases in the phosphorylation of AP-1 transcription factors correlated with a > 5-fold stimulation of expression of a 12-O-tetradecanoylphorbol-13-acetate-responsive element-chloramphenicol acetyltransferase reporter gene transiently transfected into 3T3-F442A cells. These results indicate that insulin stimulates the phosphorylation of AP-1 transcription factors and several Fos-related proteins on serine and tyrosine residues. This is associated with changes in AP-1-mediated gene expression in vivo, suggesting that AP-1 phosphorylation by insulin plays a role in insulin-regulated gene expression.
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PMID:Insulin stimulates phosphorylation of c-Jun, c-Fos, and Fos-related proteins in cultured adipocytes. 751 56

12(R)-Hydroxy-5,8,14(Z,Z,Z)-eicosatrienoic acid (12(R)-HETrE) is an arachidonic acid metabolite formed by the corneal epithelium of several species, porcine leukocytes, and human and rat epidermal cells. It is a potent, stereospecific proinflammatory and angiogenic factor and its synthesis is increased manyfold in inflamed tissues, e.g. cornea and skin. It is possible that the angiogenic activity of 12(R)-HETrE is due to a direct mitogenic effect on microvessel endothelial cells via yet to be elucidated cellular and molecular mechanisms. In the present study, we demonstrated the ability of 12(R)-HETrE to stimulate the growth of quiescent endothelial cells in a time- and concentration-dependent manner with a maximal effect at 0.1 nM. This effect was highly stereospecific since its enantiomer, 12(S)-HETrE, had no effect within the same concentration range. Northern blot analysis and transient transfection experiments with chloramphenicol acetyltransferase constructs of oncogene promoter regions demonstrated significant increases over control (0.5% fetal calf serum) in c-myc-, c-jun, and c-fos mRNA levels and expression in cells treated with 0.1 nM 12(R)-HETrE. Electrophoretic mobility shift assay of nuclear protein extracts from cells treated with 12(R)-HETrE with specific radiolabeled oligonucleotides corresponding to known transcriptional binding sites, including AP-1, AP-2, SP1, TRE, NF kappa B, TFIID, OKT1, CREB, CTF/NF1, and GRE demonstrated a markedly rapid and specific increase in the binding activity of NF kappa B and to a lesser extent, AP-1. No significant increase was observed in the binding of other transcription factors assayed as compared to control (untreated) cells. Since the protooncogenes (c-fos, c-jun, and c-myc) are immediate early response genes that are implicated in the process of cell proliferation and differentiation, and activation of certain transcription factors, in particular NF kappa B, is associated with the immediate response of the cell to an injury, we propose that 12(R)HETrE's mitogenic and angiogenic activities are mediated, in part, via the activation of NF kappa B and expression of these protooncogenes.
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PMID:Activation of nuclear factor kappa B and oncogene expression by 12(R)-hydroxyeicosatrienoic acid, an angiogenic factor in microvessel endothelial cells. 752 72

A 161-base pair fragment (AB1) approximately 10 kilobase pairs upstream of the transcription start site of the mouse heme oxygenase-1 gene functions as a basal level and inducer-dependent enhancer. AB1/chloramphenicol acetyltransferase fusion genes stably transfected into mouse hepatoma (Hepa) cells or L929 fibroblasts were activated 7-8- or 17-22-fold, respectively, after treatment of the cells with either CdCl2 or heme. The AB1 fragment is composed largely of three tandem repeats containing two conserved core elements, A and B. Part of core element A (TCCGGAGCTGTG) resembles the consensus-binding site for transcription factor AP-4, whereas core element B (GCTGAGTCANGG) includes the consensus-binding site (TGAGTCA) for the AP-1 family of transcription factors. Nuclear proteins from Hepa cells did not bind to any of the core A elements, but bound to all three copies of the core B element. AB1 derivatives with one or two mutant AP-1-binding elements exhibited reduced but measurable inducer-dependent enhancer activity, but mutation of all three AP-1-binding sites abolished activation by CdCl2 and heme and also by mercury chloride, zinc chloride, H2O2, sodium arsenate, and 12-O-tetradecanoylphorbol-13-acetate. Pretreatment of stably transfected L929 cells with protein kinase C inhibitors, but not with tyrosine kinase inhibitors or N-acetylcysteine, abrogated 12-O-tetradecanoylphorbol-13-acetate-dependent activation of the AB1/chloramphenicol acetyltransferase fusion gene. Induction by H2O2 was unaffected by the kinase inhibitors, but completely abolished by N-acetylcysteine. Heme-dependent induction was not significantly affected by any of these chemicals.
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PMID:Identification of a second region upstream of the mouse heme oxygenase-1 gene that functions as a basal level and inducer-dependent transcription enhancer. 753 29

By means of transgenic rats, we have recently shown that the GPEI enhancer of the glutathione transferase P (GST-P) gene, which has two one-base-missmatched AP-1 sites locating palindromically with three-base spacing in between, is sufficient for conferring tumor-specific activation of the gene in vivo. It is noted that there is another consensus AP-1 site near the promoter of this gene. By using seven independent transgenic rats, bearing distinct areas of the GST-P gene that are connected to the chloramphenicol acetyltransferase (CAT) coding sequence, we analyzed CAT expression in various tissues (brain, lung, liver, kidney, spleen) in these transgenic rats. We found that the ECAT gene, which has sufficient of the upstream regulatory region (approx. 2.9 kb) of the gene containing GPEI, is trans-activated in the kidney and lung of transgenic rats in a similar manner to endogenous GST-P. When either the GPEI core sequence or the AP-1 site near the promoter is deleted, CAT expression decreases to almost background level. Substitution of the GPEI core or the AP-1 site near the promoter to this silent construct (5CATGPEIcore) reconstituted CAT expression in the transgenic rats. In these rats, CAT was expressed in the brain and lung rather than in the kidney, showing a somewhat different pattern from the endogenous GST-P. In the brain tissue of the 5CATGPEIcore transgenic rat, CAT was demonstrated in the glia cells, which is consistent with endogenous GST-P expression. These results suggest that a relatively long upstream region (approx. 2.9 kb) is required for tissue-specific expression of the GST-P gene and that GST-P expression in the brain may be regulated differently from its expression in other organs.
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PMID:Tissue-specific activation of tumor marker glutathione transferase P transgenes in transgenic rats. 755 45


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