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 previously reported that in transformed mouse sarcoma cells of spontaneous origin and in revertants transfected with a fos-cat fusion, the 600-bp c-fos promoter region provides chloramphenicol acetyltransferase activity. In the present study, we investigated the binding of transcriptional factor protein(s) to a region (-503 to -361) upstream of the sis (platelet-derived growth factor)-inducible factor (SIF)-binding element. Gel electrophoresis retardation (GER) assay clearly demonstrated the appearance of strong binding activity to a newly described fragment in the 142-bp region studied. Further analysis using synthetic oligodeoxyribonucleotides and GER defined a binding region of 30 bp (AvaI-AvaII) from -503 to -472 that partially overlaps with a region known to bind fos promoter binding site 2 (FBS2). DNase I footprint analysis discovered a novel sequence in the upstream region of the c-fos promoter to which protein(s) in nuclear extracts from various mouse and human cells bind. This factor(s) is not identical to most known transcriptional factors present in the promoter region of nuclear oncogenes. A proximal part of this fragment is very conservative and contains several AP-2-like-binding sites.
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PMID:Characterization of a 142-bp fragment of the murine c-fos oncogene promoter upstream of the SIF-binding element. 819 66

Induction of glutathione S-transferase Ya and NAD(P)H:quinone reductase gene expression by a variety of chemical agents is mediated by regulatory elements, EpRE and ARE, composed of two adjacent AP-1-like binding sites and activated by Fos/Jun heterodimeric complex (AP-1). Recent studies show that chemical induction of glutathione S transferase Ya and quinone reductase gene expression is associated with an induction of c-fos and c-jun gene expression and AP-1 binding activity. In this report we present evidence that the AP-1 binding activity and the expression of chloramphenicol acetyltransferase activity from an EpRE Ya-cat gene construct are induced by an increase in intracellular oxidant levels. We observe that lowering the glutathione levels with buthionine sulfoximine, an inhibitor of gamma-glutamylcysteine synthetase, or diamide, a thiol-oxidizing agent, stimulates both basal and chemical-inducible expression of chloramphenicol acetyltransferase activity from EpRE Ya-cat and the AP-1 binding activity. Furthermore, we observe that the induction of these activities by a variety of chemical agents is inhibited by thiol compounds N-acetylcysteine and glutathione. These findings suggest that diverse chemicals that induce the AP-1 complex, leading to the AP-1-mediated transcriptional activation of glutathione S-transferase Ya gene expression, may act through a common mechanism involving the production of reactive oxygen species and depletion of reduced glutathione.
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PMID:Intracellular glutathione levels regulate Fos/Jun induction and activation of glutathione S-transferase gene expression. 826 58

Transcription of the junB gene is rapidly and transiently induced by a variety of extracellular signals. We report here that expression directed by a junB promoter/chloramphenicol acetyltransferase reporter construct (junB/CAT) is induced by fetal bovine serum, 12-O-tetradecanoylphorbol-13-acetate (TPA), epidermal growth factor (EGF), platelet-derived growth factor, and fibroblast growth factor in mouse fibroblast 3T6 cells. Deletion analysis of the promoter region of the junB gene indicates that there are at least two cis-regulatory elements that confer the capacity for serum-dependent induction. These two serum response elements (SRE1 and SRE2) are mapped between nucleotides -1451 and -1425 and between nucleotides -3100 and -2500, respectively, relative to the site of initiation of transcription. SRE1, the nucleotide sequence of which resembles that of the serum response element of the c-fos gene, is activated by TPA, platelet-derived growth factor, and fibroblast growth factor, but these growth-stimulating factors do not induce SRE2-mediated transcription. Pretreatment of the cells with phorbol dibutyrate, which reduces the level of protein kinase C activity in cells, almost completely abolishes the activation of SRE1 by TPA. Pretreatment with phorbol dibutyrate also reduces (but does not eliminate) the serum-dependent activation of SRE1. By contrast, the induction of SRE2 by serum is not affected by this pretreatment. Herbimycin A, an inhibitor of protein kinases, inhibits the activity of SRE2, but not that of SRE1. These results suggest that transcription of the junB gene can be induced by at least two distinct signaling pathways, which are mediated by SRE1 and SRE2, respectively. In addition, EGF induces expression of junB/CAT as strongly as does serum, but neither SRE1 nor SRE2 is sufficient for responsiveness to EGF.
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PMID:Two cis-regulatory elements that mediate different signaling pathways for serum-dependent activation of the junB gene. 831 5

We demonstrate that granular cerebellar neurons express functional corticotropin-releasing hormone (CRH) receptors. Activation of these receptors with CRH receptor agonists leads to a dose-dependent increase in cyclic AMP (cAMP) levels with an apparent EC50 close to 10(-9) M. Using the c-fos protooncogene as a system to evaluate genomic effects of CRH, we show that activation of CRH receptors regulates gene expression at the transcriptional level. CRH rapidly induced c-fos mRNA accumulation. Genetic studies, using chimera genes containing human c-fos promoter sequences coupled to a chloramphenicol acetyltransferase (CAT) reporter gene, confirmed and extended this observation. When protein kinase A (PKA) was specifically inactivated by gene transfer of a mutated regulatory subunit of PKA lacking cAMP binding sites, CRH-stimulated c-fos transcription was suppressed but the increase in cAMP level was not affected, indicating a key role of PKA in mediating CRH-stimulated transcription. As CRH clearly modulates gene expression via the cAMP pathway, we analyzed the genomic effect of this neurohormone on a deleted c-fos-CAT construct containing only the cAMP-responsive element (CRE) and on a heterologous promoter construct bearing the minimal palindromic consensus CRE (core sequence TGACGTCA). These minimal cAMP-responsive genes are induced by CRH. These inductions are dependent on functional PKA. Taken together, our results demonstrate the presence of functional CRH receptors in primary cerebellar cultures. Activation of these receptors stimulates gene expression via the cAMP/PKA pathway and the transacting factor CREB (cAMP-responsive element binding protein).
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PMID:Characterization and genetic analysis of functional corticotropin-releasing hormone receptors in primary cerebellar cultures. 838 Apr 41

Involucrin is one of the precursor proteins of keratinocyte cornified envelope. Although the formation of the cornified envelope is induced by tumor-promoting phorbol esters, the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the involucrin gene expression remains unknown. We have isolated a 5'-upstream region of human involucrin gene and examined its TPA-dependent promoter activity. The involucrin upstream region with the untranslated first exon was connected to chloramphenicol acetyltransferase (CAT)-involucrin promoter expression vector (INV-CAT) and was transfected into fetal rat keratinizing epidermal (FRSK) cells. The INV-CAT-transfected FRSK cells showed considerable CAT activity that was significantly augmented by the treatment of cells with TPA. FRSK cells that were transfected with a reversely oriented 5'-upstream sequence revealed little CAT activity and did not respond to TPA. The effect of TPA was significantly inhibited by the protein kinase C inhibitor 1-(5-isoquinoline-sulfonyl)-2-methyl piperazine dihydrochloride (H-7). Other protein kinase C activators (1-oleoyl-2-acetylglycerol and mezerein) also induced the INV-CAT promoter activity, whereas 4-O-methyl phorbol myristate acetate, a very weak protein kinase C activator, had only a slight effect. Analysis of the nucleotide sequence of the 5'-upstream region detected several 5'-TGANTCAA-3' sequences that are highly conserved TPA-response elements (TRE). Cotransfection of both c-jun and c-fos expression vectors with the INV-CAT vector into FRSK cells resulted in increased CAT activity. Cotransfection of either the c-jun or c-fos vector singly with the INV-CAT vector into FRSK cells had negligible effects. Dexamethasone significantly inhibited the TPA-induced promoter activity in the INV-CAT-transfected FRSK cells. These results indicate that involucrin gene expression is positively controlled by TPA through the activation of the protein kinase C/TRE system.
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PMID:Analysis of the 5'-upstream promoter region of human involucrin gene: activation by 12-O-tetradecanoylphorbol-13-acetate. 838 Aug 29

c-fos gene expression in two types of mouse sarcoma cells of spontaneous origin and in revertants to pseudonormal phenotype has been investigated. In the latter cells the content of c-fos mRNA is similar to that in normal fibroblasts. Activity of transcription factors interacting with the regulatory elements, SRE, DSE and TRE, in the c-fos promoter do not correlate with the c-fos mRNA concentration. However, experiments with cells transformed with the indicator plasmid, fos-CAT, showed that the 600 bp c-fos promoter region provides the chloramphenicol acetyltransferase activity correlating with c-fos mRNA expression in cell revertants to a pseudonormal phenotype.
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PMID:c-fos gene expression in cell revertants from a transformed to a pseudonormal phenotype. 842 Aug 1

The expression of thrombospondin 1 (TSP 1), a member of the TSP gene family, is rapidly induced by growth factors. We tested the ability of human TSP 1-chloramphenicol acetyltransferase constructs to respond to serum in stably transfected NIH-3T3 cells. Two transcriptional elements in the TSP 1 promoter, a distal element at -1280 and a proximal element at -65, were required for the response of the human TSP 1 gene to serum. The distal element contains the 5'-CC(A + T)6GG-3' consensus sequence characteristic of a serum-response element (SRE). Deletions or mutations in this element reduced the serum response of the TSP 1 gene by 80-90%. In gel-shift assays, the -1280 element and the c-fos SRE cross-competed, whereas their functional and binding mutants did not. The proximal element contains the sequence 5'-GGCCAATGGG-3', which closely resembles the consensus binding motif for the CCAAT-binding factor NF-Y (CBF, CP1, alpha CP1). Deletions or mutations in this element also reduced the serum response by 80-90%. Methylation interference analysis of the -65 region identified a pattern of contacts with nuclear factors resembling that for NF-Y, and an NF-Y-binding site and the proximal TSP 1 element cross-competed in gel-shift assays, whereas their binding mutants did not. Finally, an abbreviated TSP 1 promoter/5'-flank, containing the SRE- and NF-Y-binding sites, mediated a serum response that was close in magnitude to that of the parent promoter. We conclude that the serum response of the human TSP 1 gene requires the coordinated function of an SRE- and NF-Y-binding site.
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PMID:A serum response element and a binding site for NF-Y mediate the serum response of the human thrombospondin 1 gene. 844 76

The present studies have examined the effects of mitogens on induction of early response gene expression in normal peripheral blood T and Jurkat cells. Pokeweed mitogen (PWM) or anti-CD3 significantly increases c-jun messenger RNA (mRNA) levels in T cells. This transient PWM-related increase in c-jun transcripts is maximal after 15 to 30 minutes of exposure of T cells to PWM. PWM induces c-jun gene expression in a concentration-dependent manner. Moreover, PWM similarly induces expression of other genes coding for leucine zipper transcription factors, ie, jun-B and c-fos. Nuclear run on assays demonstrate that PWM treatment is associated with an increased rate of c-jun gene transcription. Transient expression assays with c-jun promoter fragments linked to the chloramphenicol acetyltransferase gene suggest that the PWM-induced increase in transcription is mediated by the AP-1 transcription factor complex. Moreover, treatment of T cells with actinomycin D to block further transcription before their culture with PWM suggests that the increase in c-jun gene expression by PWM is also regulated at least in part by a posttranscriptional mechanism. Cycloheximide does not alter c-jun mRNA induction by PWM. Finally, given that PWM induces B-cell differentiation in an interleukin-6 (IL-6)-mediated, T-cell-dependent manner, the relationship of c-jun and IL-6 gene expression in PWM-stimulated T cells was examined. The induction of IL-6 mRNA in T cells stimulated by PWM occurs after maximal induction of c-jun mRNA, at a time when the latter is no longer detectable. These findings suggest that PWM induces c-jun gene expression in T cells by a transcriptional and posttranscriptional mechanism and that AP-1 confers PWM inducibility of this gene. Because the IL-6 promoter has several potential transcriptional control elements, one of which is an AP-1-binding site, future experiments will evaluate the role of c-jun in the regulation of PWM-induced IL-6 synthesis by T cells.
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PMID:Regulation of c-jun gene expression in human T lymphocytes. 845 1

We have previously documented that glucocorticoids suppress the proliferation of BDS1 hepatoma cells, a rat epithelial tumor cell line derived from minimal deviation Reuber H35 hepatoma cells. Flow cytometry demonstrated that, after treatment with the synthetic glucocorticoid dexamethasone, the growth of an asynchronous population of BDS1 cells was arrested within one cell cycle which resulted in an accumulation of cells with a G1-G0-like DNA content. Consistent with a glucocorticoid-induced block early in the G1 phase of the cell cycle, propidium iodide flow cytometry revealed that addition of dexamethasone up to 2 h after release from contact inhibition prevented BDS1 hepatoma cells from entering S phase, whereas dexamethasone treatment after 2 h had no effect on the entry of cells into S phase. Moreover, dexamethasone treatment did not prevent BDS1 cells from entering S phase after release from synchronization at the G1-S boundary by a double thymidine block. Analysis of DNA content, [3H]-thymidine incorporation, and autoradiography of [3H]-thymidine-labeled nuclei revealed that, after release from dexamethasone, BDS1 cells synchronously reinitiated cell cycle progression and entered S phase 8 h after hormone withdrawal. Northern blot analysis demonstrated that the level of transcripts encoding the G1 marker genes CYL-1 and CYL-2 G1 cyclins peaked 4 h after dexamethasone withdrawal. Dexamethasone induced a 20-fold increase in the level of c-jun mRNA which was reversed after hormone withdrawal, whereas expression of c-fos transcripts remained at a low level during the time course of hormone treatment and withdrawal. Transient transfections with a collagenase-chloramphenicol acetyltransferase reporter gene showed that dexamethasone inhibited 12-O-tetradecanoylphorbol-13-acetate-inducible, but not basal, AP-1 transcription factor activity. Our results demonstrate that glucocorticoids reversibly induce an early G1 block in cell cycle progression of an epithelial tumor cell line that occurs with a coordinate elevation in the expression of c-jun transcripts.
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PMID:Glucocorticoids reversibly arrest rat hepatoma cell growth by inducing an early G1 block in cell cycle progression. 846 59

The murine alpha B-crystallin/small heat shock protein gene is expressed at high levels in the lens and at lower levels in the heart, skeletal muscle, and numerous other tissues. Previously we have found a skeletal-muscle-preferred enhancer at positions -427 to -259 of the alpha B-crystallin gene containing at least four cis-acting regulatory elements (alpha BE-1, alpha BE-2, alpha BE-3, and MRF, which has an E box). Here we show that in transgenic mice, the alpha B-crystallin enhancer directs the chloramphenicol acetyltransferase reporter gene driven by the alpha B-crystallin promoter specifically to myocardiocytes of the heart. The alpha B-crystallin enhancer was active in conjugation with the herpes simplex virus thymidine kinase promoter/human growth hormone reporter gene in transfected rat myocardiocytes. DNase I footprinting and site-specific mutagenesis experiments showed that alpha BE-1, alpha BE-2, alpha BE-3, MRF, and a novel, heart-specific element called alpha BE-4 are required for alpha B-crystallin enhancer activity in transfected myocardiocytes. By contrast, alpha BE-4 is not utilized for enhancer activity in transfected lens or skeletal muscle cell lines. Alpha BE-4 contains an overlapping heat shock sequence and a reverse CArG box [5'-GG(A/T)6CC-3']. Electrophoretic mobility shift assays with an antibody to serum response factor and a CArG-box-competing sequence from the c-fos promoter indicated that a cardiac-specific protein with DNA-binding and antigenic similarities to serum response factor binds to alpha BE-4 via the reverse CArG box; electrophoretic mobility shift assays and antibody experiments with anti-USF antiserum and heart nuclear extract also raised the possibility that the MRF E box utilizes USF or an antigenically related protein. We conclude that the activity of the alpha B-crystallin enhancer in the heart utilizes a reverse CArG box and an E-box-dependent pathway.
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PMID:Regulation of the murine alpha B-crystallin/small heat shock protein gene in cardiac muscle. 852 75


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