Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epithelium-specific transcription factor, ERT/ESX/ESE-1/ELF3, binds to the TGF-beta RII promoter in a sequence specific manner and regulates its expression. In this study, we investigated whether ERT could regulate endogenous TGF-beta RII expression in Hs578t breast cancer cells. Analyses of the Hs578t parental cell line revealed low RII mRNA expression and resistance to the growth inhibitory effects of TGF-beta. Infection of this cell line with a retroviral construct expressing ERT induced higher levels of endogenous RII mRNA expression and protein expression relative to cells infected with chloramphenicol acetyltransferase (CATneo) as a control. Relative to control cells, the ERTneo-expressing Hs578t cells show approximately a 50% reduction in cell growth in the presence of exogenous TGF-beta1, as well as a fourfold higher induction of activation in transient transfection assays using the 3TP-luciferase reporter construct. When transplanted into athymic mice, ERT-expressing Hs578t cells showed decreased and delayed tumorigenicity compared with control cells. This data strongly suggests that ERT plays an important role as a transcriptional activator of TGF-beta RII expression, and that deregulated ERT expression may play a critical role in rendering Hs578t human breast cancer cells insensitive to TGF-beta's growth inhibitory effects.
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PMID:Over-expression of ERT(ESX/ESE-1/ELF3), an ets-related transcription factor, induces endogenous TGF-beta type II receptor expression and restores the TGF-beta signaling pathway in Hs578t human breast cancer cells. 1064 90

The consensus TGF-beta element (TGCCCACGGCCAG) located at approximately -161Obp from the start site of transcription of the rat pro alpha1(I) collagen gene has recently been shown to be required for the basal promoter activity of this gene (Meisler et al., J. Cell Biochem. 75: 196, 1999). Site directed mutation of this TGF-beta element resulted in almost complete abolishment of the basal promoter activity of the fibroblasts transfected with the 3.6 ColCat plasmid which contains a 3.6 kb portion of the 5' flanking region of the rat pro alpha1(I) collagen gene linked to the reporter gene, chloramphenicol acetyltransferase (CAT). Southwestern analysis of the nuclear protein binding to the TGF-beta element revealed a 34,000 Da complex while after UV-crosslinking, studies revealed a TGF-beta element nuclear protein complex of 82,000 Da (Ritzenthaler et al., J. Biol. Chem. 268: 13625, 1993). Thus, a multiple protein TGF-beta DNA element complex may exist which may promote the transcription of the rat pro alpha1(I) collagen gene. Since literature findings indicate that a nuclear factor interacts with an SP1-like binding site of the human pro alpha1(I) collagen promoter and an AP-1 binding sequence has been shown to be involved in the regulation of the human pro alpha2(I) collagen gene and both these binding sequences are TGF-beta1 responsive, we determined whether the TGF-beta element located in the 5' flanking region of the rat pro alpha1(I) collagen gene formed complexes with either of these nuclear factors or both.
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PMID:Human SP1 but not human AP1 binding to the TGF-beta element in the 5' flanking region of the rat PROalpha1(I) collagen gene. 1125 9

We report that exposure of mouse embryonic fibroblasts to transforming growth factor beta-1 (TGFbeta-1) (5 ng/ml) results in a strong activation of p8 mRNA expression that precedes the induction of cell growth. Involvement of the p8 promoter in the regulation was demonstrated by using a p8-chloramphenicol acetyltransferase construct. We therefore speculated that p8 might be a mediator of TGFbeta-1 in these cells. The incorporation of [(3)H]thymidine on treatment with TGFbeta-1 was indeed significantly higher in p8(+/+) fibroblasts than in p8(-/-) fibroblasts. Smad transcriptional activity was used as marker of the TGFbeta-1 signalling pathway, to probe the lower p8(-/-) response to TGFbeta-1. Two Smad-binding elements (SBEs)-luciferase constructs were transfected into p8(-/-) and p8(+/+) embryonic fibroblasts before treatment with TGFbeta-1. A lower level of Smad transactivation was observed in p8(-/-) embryonic fibroblasts, under basal conditions and after stimulation with TGFbeta-1. To test whether Smad underexpression in p8(-/-) cells was actually due to p8 depletion, p8(-/-) embryonic fibroblasts were transfected with a human p8 expression plasmid together with an SBE-luciferase construct. The expression of p8 restored Smad transactivation in unstimulated and TGFbeta-1-treated cells to the level found in p8(+/+) cells. We concluded that TGFbeta-1 activates p8 expression, which in turn enhances the Smad-transactivating function responsible for TGFbeta-1 activity.
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PMID:Transforming growth factor beta-1 enhances Smad transcriptional activity through activation of p8 gene expression. 1141 56

Surfactant protein B (SP-B) is a developmentally and hormonally regulated lung protein that is required for normal surfactant function. We generated transgenic mice carrying the human SP-B promoter (-1,039/+431 bp) linked to chloramphenicol acetyltransferase (CAT). CAT activity was high in lung and immunoreactive protein localized to alveolar type II and bronchiolar epithelial cells. In addition, thyroid, trachea, and intestine demonstrated CAT activity, and each of these tissues also expressed low levels of SP-B mRNA. Developmental expression of CAT activity and SP-B mRNA in fetal lung were similar and both increased during explant culture. SP-B mRNA but not CAT activity decreased during culture of adult lung, and both were reduced by transforming growth factor (TGF)-beta(1). Treatment of adult mice with intratracheal bleomycin caused similar time-dependent decreases in lung SP-B mRNA and CAT activity. These findings indicate that the human SP-B promoter fragment directs tissue- and lung cell-specific transgene expression and contains cis-acting elements involved in regulated expression during development, fetal lung explant culture, and responsiveness to TGF-beta and bleomycin-induced lung injury.
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PMID:Human surfactant protein B promoter in transgenic mice: temporal, spatial, and stimulus-responsive regulation. 1183 32

Transcriptional repression of the TGF-beta type II receptor (RII) is one of the mechanisms leading to TGF-beta resistance. The newly identified epithelium-specific ets transcription factor ERT/ESX/ESE-1 binds to the TGF-beta RII promoter and induces promoter activity. This study aims to investigate the mechanisms underlying development of ERT-mediated TGF-beta resistance using antisense ERT oligonucleotide. We performed Northern blot analysis of TGF-beta RII expression in human colon cancer cell line, RKO, after transfecting these cells with MFG-antisense-ERT retroviral construct. The plasmid containing the chloramphenicol acetyltransferase (CAT) gene alone was used as the control. The amount of TGF-beta RII mRNA appears to be poor in RKO cells expressing antisense ERT compared with both parental RKO and control cells. In conclusion, transfection of MFG-antisense-ERT construct into the colon cancer cell line could result in lower levels of TGF-beta RII mRNA expression, which means that ERT mediates the expression of TGF-beta RII and the transcriptional inhibition of ERT could be a one of the mechanisms of colonic carcinogenesis. More in vitro and in vivo studies should be required to evaluate this treatment in clinical setting.
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PMID:Effect of ets-related transcription factor (ERT) on transforming growth factor (TGF)-beta type II receptor gene expression in human cancer cell lines. 1458 9

Oncostatin M (OSM) regulates expression of various genes in connective tissue (CT) cells, including tissue inhibitor of metalloproteinases-1 (TIMP-1). In mouse fibroblast cell lines MLg, NIH 3T3 and primary mouse lung fibroblasts (MLF), murine OSM (muOSM) stimulated high TIMP-1 mRNA expression in comparison to leukemia inhibitory factor (LIF), epidermal growth factor (EGF), interleukin (IL)-1beta and transforming growth factor (TGF)beta. In cell signaling, muOSM induced strong phosphorylation of extracellular-signal regulated protein kinase (Erk) 1/2, p38 and Akt in addition to phosphorylation of signal transducer and activator of transcription (STAT) 1, STAT3 and STAT5 within 15 min. LIF and TGFbeta had no such effects. EGF stimulated comparable or lower Erk1/2, p38 and Akt phosphorylation while IL-1beta induced p38 phosphorylation in the fibroblast cell lines. The Erk1/2 inhibitor PD98059 and the p38 inhibitor SB203580 inhibited TIMP-1 mRNA response to muOSM, whereas the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 enhanced the TIMP-1 mRNA response in NIH 3T3 and MLg cells. PD98059 and SB203580, but not LY294002, also inhibited fold induction of a chloramphenicol acetyltransferase (CAT) reporter gene driven by a minimal TIMP-1 promoter that contained a proximal activator protein-1 (AP-1) site. Co-transfection with JunB or c-Jun expression vector in NIH 3T3 cells caused marked transactivation of the TIMP-1 promoter/CAT reporter gene. muOSM caused a rapid increase of JunB and c-Jun protein in NIH 3T3 cells. PD98059 partially inhibited the increase of JunB, but not c-Jun, whereas SB203580 did not induce detectable changes in expression of either AP-1 factor in response to muOSM. These results demonstrate that Erk1/2 and p38 contribute to the elevation of muOSM induced TIMP-1 expression, but PI3K does not, and suggest that Erk1/2 does so by enhancing JunB expression.
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PMID:Mitogen-activated protein kinases Erk1/2 and p38 are required for maximal regulation of TIMP-1 by oncostatin M in murine fibroblasts. 1524 7

Type IV collagen is present ubiquitously in basement membranes. A bifunctional promoter regulates the expression of the alpha1/alpha2 genes, and the alpha3/alpha4 and the alpha5/alpha6 genes are also considered to be regulated by putative bifunctional promoters. Unlike the other type IV collagen chains, the alpha5(IV) and alpha6(IV) chains do not always co-localize and are present in distinct basement membranes. To address such dichotomy in the alpha5(IV) and alpha6(IV) gene regulation, we cloned a mouse genomic DNA fragment containing the promoter region between the two transcription start sites of these genes and we then placed this putative promoter sequence between the chloramphenicol acetyltransferase and Luciferase reporter genes, so that these genes would be transcribed in opposite directions in this unique construct. Glomerular endothelial cells and mesangial cells generate the kidney glomerular basement membrane, which always contains the alpha5(IV) chain but not the alpha6(IV) chain. In contrast, the basement membranes of Bowman's capsule and distal tubuli (produced by the tubular epithelial cells) contain the alpha6(IV) chain. We demonstrate that, in response to TGF-beta (transforming growth factor beta), epidermal growth factor, vascular endothelial growth factor and platelet-derived growth factor, expression from the alpha5(IV) gene is significantly enhanced in the glomerular endothelial cells and mesangial cells, but not expression from the alpha6(IV) gene. In contrast, the expression from the alpha6(IV) gene, and not that from the alpha5(IV) gene, was significantly enhanced in response to growth factors in the tubular epithelial cells. Our results demonstrate that the proximal bifunctional promoter regulates the expression of the alpha5(IV) and alpha6(IV) genes in a cell-specific manner and offers the first demonstration of the promoter plasticity in growth factor regulation of type IV collagen genes in different tissues of the body.
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PMID:Bifunctional promoter of type IV collagen COL4A5 and COL4A6 genes regulates the expression of alpha5 and alpha6 chains in a distinct cell-specific fashion. 1559 79


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