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)

Retinoic acid (RA) and epidermal growth factor (EGF) regulate growth and differentiation of epithelial cells. RA has both direct and indirect effects on gene expression. Direct effects result from modulation of the transcriptional activity of genes, which contain RA response elements (RARE) recognized by trans-acting nuclear RA receptors (RARs). A second indirect mechanism for the modulatory effects of RA is by the induction or repression of growth factors and growth factor receptors. There is evidence for functional interactions between RA and the EGF receptor (EGFR). RA enhances the proliferative response of cultured keratinocytes to EGF, increases the number of EGFRs on the surface of some cells, and induces EGFR promoter activity in most cells. In contrast, immunoprecipitation, Northern blot, and nuclear run-on analysis described in this paper show that RA suppresses EGFR synthesis at the transcriptional level in human epidermoid carcinoma ME180 cells. Deletion analysis of EGFR gene promoter mutants linked to the chloramphenicol acetyltransferase gene revealed the existence of a region of the promoter, -771 to -384, which is responsive to RA. Gel retardation data indicated that a cell-type nuclear protein which binds to this novel element is suppressed by RA in a dose-dependent manner. This decrease coincides with a decreased steady-state level of RAR-gamma mRNA. These data strongly suggest that the EGFR promoter is regulated by RAR-gamma, which itself is under the control of RA. Other cell-specific trans-acting factors may be involved in this regulation.
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PMID:Transcriptional control of epidermal growth factor receptor by retinoic acid. 151 68

Deregulated c-fos expression in the rat pheochromocytoma cell line, PC-12, causes pronounced downregulation of nerve growth factor (NGF)-induced c-fos and c-jun activation, accompanied by a block in NGF-induced differentiation of PC-12 cells. The FOS-expressing PC-12 cells were exposed to diverse agents such as NGF, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), dibutyryl cyclic adenosine 3',5' monophosphate (db cAMP), and Ca-ionophore; and the expression of egr-1, c-fos, c-jun, jun-B, and jun-D was analyzed. Pronounced downregulation of c-fos, c-jun, and--to a lesser extent--jun-B was observed on treatment with NGF, bFGF, db cAMP, and Ca-ionophore, whereas EGF-induced activation of these early response genes was not inhibited in FOS-expressing PC-12 cells. Ca-ionophore- and db cAMP-induced egr-1 activation in PC-12 fos cells was completely inhibited. Both parent and PC-12 fos cells expressed similar high basal levels of jun-D, whose expression was the least regulatable by all of these agents. Transfection of fos promoter-chloramphenicol acetyltransferase (promoter-CAT) plasmid into these stable FOS-expressing PC-12 cells revealed that these effects are exerted at the fos promoter level.
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PMID:Transcriptional regulation of early growth response genes in FOS-expressing PC-12 cells. 196 43

We used a dominant inhibitory mutation of c-Ha-ras which changes Ser-17 to Asn-17 in the gene product p21 [p21(Asn-17)Ha-ras] to investigate ras function in mitogenic signal transduction. An NIH 3T3 cell line [NIH(M17)] was isolated that displayed inducible expression of the mutant Ha-ras gene (Ha-ras Asn-17) via the mouse mammary tumor virus long terminal repeat and was growth inhibited by dexamethasone. The effect of dexamethasone induction on response of quiescent NIH(M17) cells to mitogens was then analyzed. Stimulation of DNA synthesis by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) was completely blocked by p21(Asn-17) expression, and stimulation by serum, fibroblast growth factor, and platelet-derived growth factor was partially inhibited. However, the induction of fos, jun, and myc by EGF and TPA was not significantly inhibited in this cell line. An effect of p21(Asn-17) on fos induction was, however, demonstrated in transient expression assays in which quiescent NIH 3T3 cells were cotransfected with a fos-cat receptor plasmid plus a Ha-ras Asn-17 expression vector. In this assay, p21(Asn-17) inhibited chloramphenicol acetyltransferase expression induced by EGF and other growth factors. In contrast to its effect on DNA synthesis, however, Ha-ras Asn-17 expression did not inhibit fos-cat expression induced by TPA. Conversely, downregulation of protein kinase C did not inhibit fos-cat induction by activated ras or other oncogenes. These results suggest that ras proteins are involved in at least two parallel mitogenic signal transduction pathways, one of which is independent of protein kinase C. Although either pathway alone appears to be sufficient to induce fos, both appear to be necessary to induce the full mitogenic response.
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PMID:Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells. 211 93

The transcriptionally active RVL3-VL30 element contains a triple repeat of TGACTCC, a sequence nearly identical to the AP-1 binding site. However, 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation was unable to elicit chloramphenicol acetyltransferase (CAT) expression from a construct containing these AP-1-like sequences upstream of the thymidine kinase promoter present in pTES. Endothelin, which activates protein kinase C (pkC) and elevates intracellular Ca2+ in Rat-1 cells, was effective in stimulating CAT expression from the VL30-pTES construct. We attempted to assess the relative importance of these second messenger systems by stimulating each pathway separately with exogenous agonists. We determined that neither stimulation of pkC by the tumor promoter TPA nor elevation of intracellular Ca2+ by the tumor promoter thapsigargin was sufficient to stimulate CAT expression from the VL30-pTES vector. When combined, the two tumor promoters induced a synergistic increase in CAT expression. Our data indicate that elevation of intracellular Ca2+ by thapsigargin was not required for full activation of pkC by TPA. First, TPA was able to stimulate expression of other genes in Rat-1 cells, indicating full activation of pkC. Second, thapsigargin synergized effectively with epidermal growth factor to stimulate CAT activity from the VL30-pTES construct in cells depleted of pkC activity by chronic TPA treatment. The permissive effects of thapsigargin on gene expression were also observed for an endogenous gene, transin/stromelysin. The permissive effects of elevated intracellular Ca2+ levels may represent a general mechanism for the stimulation of some genes by pkC-mediated pathways.
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PMID:Two tumor promoters, 12-O-tetradecanoylphorbol-13-acetate and thapsigargin, act synergistically via distinct signaling pathways to stimulate gene expression. 212 50

Release of prolactin from both normal pituitary cells and rat pituitary tumor (GH) cells is an osmotic process that is dependent upon chloride. The long term growth rate of GH-cells in medium in which chloride was exchanged with isethionate was completely normal, but, by 48 h, isethionate substitution resulted in a 70% decrease in the concentration of internal and secreted prolactin. Isethionate caused a much smaller reduction in growth hormone production (less than 20%). These results suggest that exchange of chloride with isethionate is inhibiting the synthesis of prolactin. Reduction of intracellular levels of prolactin in cells grown in isethionate-containing medium was evident by 30 h, and the level of prolactin was reduced 92% at 96 h. This reduction in the internal concentrations of prolactin was reversed when the cells were returned to normal medium containing chloride with a t1/2 of 48 h. Addition of epidermal growth factor and the calcium channel agonist BAY K 8644 to cells in medium containing chloride increased internal prolactin by 400%, and isethionate exchange reduced the response by 85%. To confirm that isethionate exchange was inhibiting the synthesis of prolactin, mRNA concentrations for prolactin and actin were determined. Both basal and hormone-stimulated levels of prolactin mRNA were reduced 70 to 90% by isethionate exchange, while actin mRNA levels did not change. To determine whether the effect of isethionate was at the level of gene transcription, GH-cells were transfected with a prolactin-chloramphenicol acetyltransferase fusion gene and chloramphenicol acetyltransferase expression was assessed using cells in chloride and isethionate-containing media. Both basal and hormone-stimulated synthesis of chloramphenicol acetyltransferase driven by the prolactin promoter was inhibited by isethionate exchange. These studies demonstrate that exchange of medium chloride with isethionate inhibits the synthesis of prolactin at the level of transcription.
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PMID:Prolactin synthesis in cultured pituitary cells is chloride-dependent. 246 Apr 42

The possible role of the catalytic subunit of the cAMP-dependent protein kinase in mediating the regulation of prolactin gene transcription has been investigated through the use of a synthetic gene encoding the heat-stable inhibitor of the cAMP-dependent protein kinase. To assess the effects of protein kinase inhibitor expression on cAMP induction of prolactin gene transcription, a marker gene containing the rat prolactin promoter and adjacent 5'-flanking sequences linked to the bacterial chloramphenicol acetyltransferase gene was cotransfected with a protein kinase inhibitor-expression vector. The results demonstrate that the protein kinase inhibitor-expression vector reduced both basal and cAMP-stimulated expression of the cotransfected prolactin-chloramphenicol acetyltransferase gene. A mutant protein kinase inhibitor-expression vector, coding for an inactive inhibitor protein, did not inhibit basal or cAMP-stimulated prolactin gene transcription. Furthermore, the protein kinase inhibitor-expression vector did not inhibit zinc induction of the metallothionein promoter. Analysis of protein kinase activity in transfected cells demonstrated that the protein kinase inhibitor expression vector reduced cAMP-dependent protein kinase activity but did not reduce protein kinase C activity. Nuclease protection experiments confirmed that the effects of the inhibitor vector involved changes in correctly initiated transcripts produced from the prolactin promoter. Surprisingly, the protein kinase inhibitor-expression vector reduced the effects of several different agents including epidermal growth factor, thyrotropin-releasing hormone, phorbol esters, and estrogen on prolactin gene expression to the same extent as it altered cAMP effects.
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PMID:A protein kinase inhibitor gene reduces both basal and multihormone-stimulated prolactin gene transcription. 253 42

The ability of an upstream element of the rat PRL gene to permit transcriptional regulation in response to several different hormones has been examined. To test the ability of specific DNA sequences to mediate hormone responsiveness, DNA fragments were subcloned upstream of a thymidine kinase-chloramphenicol acetyltransferase fusion gene and transferred into GH3 pituitary tumor cells. Initially, fragments representing a distal enhancer element (positions -1713 to -1495) and a more proximal element (positions -292 to -38) were tested. The results demonstrate that the distal enhancer permits cAMP, TRH, epidermal growth factor (EGF), and estradiol to stimulate expression of the thymidine kinase-chloramphenicol acetyltransferase gene. The proximal element permitted fusion gene regulation in response to cAMP, TRH, EGF, and phorbol esters. For the cAMP, TRH, and EGF responses, the distal element permitted responses approximately equal to or greater than responses conferred by the proximal PRL gene fragment. The response of the distal element to cAMP and TRH was more than additive with the response to estradiol, suggesting that the estrogen response element is distinct but may interact cooperatively with the other hormone response elements. Mutation of the estrogen-responsive element abolished both the response to estrogen and the cooperative response with cAMP, but not the response to cAMP itself. Mutation of a sequence involved in basal enhancer activity of the distal element reduced both basal transcription and the response to cAMP. These results suggest that the distal enhancer sequence of the PRL gene contains, in addition to an estrogen response element, elements that confer responsiveness to cAMP, TRH, and EGF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The distal enhancer region of the rat prolactin gene contains elements conferring response to multiple hormones. 253 91

The regulation of gastrin gene transcription was studied in GH4 pituitary cells transfected with constructs comprised of the first exon of the human gastrin gene and various lengths of 5' regulatory sequences ligated upstream of the reporter gene chloramphenicol acetyltransferase. Gastrin reporter gene activity in GH4 cells was equal to the activity of a reporter gene transcribed from the endogenously expressed growth hormone promoter. The effect of a variety of peptides on gastrin gene transcription including epidermal growth factor (normally present in the gastric lumen), gastrin-releasing peptide, vasoactive intestinal peptide, and somatostatin (present in gastric nerves) was assessed. Epidermal growth factor increased the rate of gastrin transcription almost 3-fold, whereas thyrotropin-releasing hormone and vasoactive intestinal peptide increased gastrin transcription 2- and 1.5-fold, respectively. Gastrin-releasing peptide, a peptide that strongly stimulates gastrin release, weakly increased gastrin transcription (1.3-fold). Somatostatin inhibited the increase in gastrin transcription induced by epidermal growth factor, thyrotropin-releasing hormone, and vasoactive intestinal peptide. Constructs containing various lengths of 5' regulatory sequences defined a response element -40 to -82 base pairs (bp) 5' to the transcription initiation site. This 40-bp sequence contains Sp1 and AP2 binding sites, which suggests that epidermal growth factor and thyrotropin-releasing hormone stimulate gastrin gene transcription through transcription factors that bind to Sp1 and/or AP2 motifs.
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PMID:Regulation of the gastrin promoter by epidermal growth factor and neuropeptides. 256 64

Stromelysin is a member of a gene family of metalloproteinases involved in extracellular matrix remodeling in normal and diseased processes. Primary cultures of rheumatoid synovial cells produce large amounts of metalloproteinase mRNA and proteins. We cloned a cDNA for human stromelysin from a rheumatoid synovial cell cDNA library, and we used the cDNA to isolate the gene for human stromelysin and a related gene, stromelysin 2. We sequenced parts of the genes and found that both are contained on approximately 14 kilobase pairs of DNA. Using an exon-containing fragment of the stromelysin 2 genomic clone as a specific probe in Northern blot analysis, we demonstrate the differential expression of stromelysin and stromelysin 2 in rheumatoid synovial cells, human foreskin fibroblasts, and rabbit synovial fibroblasts. In addition, using chimeric constructs of the stromelysin promoter linked to the bacterial gene chloramphenicol acetyltransferase (CAT), we show that the elements required for the tumor promoter phorbol myristate acetate (PMA), epidermal growth factor (EGF), and interleukin 1 beta (IL-1 beta) induction are contained on a 307 base pair fragment which includes approximately 270 base pairs (bp) of 5'-flanking DNA. The cloning of the human stromelysin and stromelysin 2 genes, the documentation of their differential expression, and the identification of transcriptional regulatory regions in the stromelysin gene will facilitate the study of metalloproteinase gene expression in normal processes and in diseases such as rheumatoid arthritis.
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PMID:Cloning of the genes for human stromelysin and stromelysin 2: differential expression in rheumatoid synovial fibroblasts. 260 16

The stromelysin gene encodes a potent tissue-degrading proteinase whose activity is important in tissue-remoldeling processes such as wound healing, the inflammatory reaction, rheumatoid arthritis, tumor invasion, and possibly embryonic development. In light of the ability of interleukin-1 to amplify, and ability of glucocorticoids to attenuate the inflammatory response, we tested interleukin-1 and dexamethasone for regulatory effects on stromelysin gene expression. We report that interleukin-1 induces the stromelysin gene, and dexamethasone diminishes the level of induction by interleukin-1, epidermal growth factor, phorbol ester, and cAMP elevation (elicited by cholera toxin). Similar responses are conferred upon a chloramphenicol acetyltransferase coding sequence by a 700-base pair stromelysin 5'-flanking fragment, implying transcription regulation by sequence elements in this region.
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PMID:Transcription from the stromelysin promoter is induced by interleukin-1 and repressed by dexamethasone. 282 88


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