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)

Transforming growth factor TGF-beta 2 is encoded by multiple mRNA transcripts of 5.8, 5.1, 4.0, 3.8, and 2.8 kilobase pairs (kb) that are expressed in various human and monkey cells. Northern blot analysis using genomic fragments of DNA was used to demonstrate that some of this size heterogeneity is due to differences in the length of the 5'-untranslated region. Probes that were colinear with the first 600 nucleotides of the 5'-untranslated region detected only the 5.8-, 4.0-, and 3.8-kb transcripts. In order to identify DNA elements that regulate the transcription of these mRNA transcripts, deletion constructs of 5'-flanking DNA were ligated to the coding region for chloramphenicol acetyltransferase (CAT) and analyzed for promoter activity in several cell lines. Sequences responsible for putative enhancer and silencer regions were identified between -778 and -40 relative to the transcription initiation site. Addition of a cyclic AMP-responsive element/activating transcription factor-like element at -74 resulted in a 5-10-fold increase in CAT activity over that expressed with a construct that contained only the TATA box. This increase in CAT activity was suppressed by the addition of DNA sequences between -257 and -187, whereas sequences between -778 and -257 stimulated CAT activity. Point mutations within the ATF binding site at -74 resulted in a marked decrease in CAT expression. Cotransfection with ATF-1 or ATF-2 expression plasmids resulted in both dose-dependent stimulatory and inhibitory activities that were cell type-dependent. These studies identify multiple transcription initiation sites for TGF-beta 2 and demonstrate that transcription from one of these promoters is dependent upon an ATF binding site located 5' of the TATA box.
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PMID:Identification of an activating transcription factor (ATF) binding site in the human transforming growth factor-beta 2 promoter. 140 Mar 10

The promoter regions of the three mammalian transforming growth factor-beta genes (TGF-beta s 1, 2, and 3) have been recently cloned and characterized. The sequences show little similarity, suggesting different mechanisms of transcriptional control of these genes. To study differences in transcriptional regulation of mammalian and avian TGF-beta, we have cloned and sequenced the 5'-flanking region of chicken TGF-beta 3. Characterization of this region showed a TATA box and cAMP-responsive element (CRE) and AP-2 binding site consensus sequences starting at 12 and 28 base pairs, respectively, upstream from the TATA box. Moreover, four additional AP-2-like sites, 10 binding sites for the transcription factor Sp1, as well as two AP-1-like sites were also identified. Except for 32 base pairs of identity centered around the TATA box and CRE site and four other relatively small regions of identity, the chicken TGF-beta 3 promoter was found to be structurally very different from the human TGF-beta 3 promoter. Promoter fragments were cloned into a chloramphenicol acetyltransferase reporter plasmid to study functional activity. Basal transcriptional activity of the promoter was regulated in quail fibrosarcoma QM7 cells and in human adenocarcinoma A375 cells by multiple upstream elements including the TATA, CRE, and AP-2 sites. As in the human TGF-beta 3 promoter, the CRE site showed activation by forskolin, an effect which could be shown by expression of TGF-beta 3 mRNA in cultured chicken and quail cells as well. Our results indicate a complex pattern of transcriptional regulation of the chicken TGF-beta 3 gene and suggest that differences in the regulation of expression of the genes for mammalian and avian TGF-beta 3 may result in part from the unique structure of their 5'-flanking regions.
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PMID:Identification and characterization of the chicken transforming growth factor-beta 3 promoter. 140 6

Previous studies have shown that EC cells do not express detectable levels of TGF-beta 2 or its mRNA until they differentiate. This suggested that differentiation influences the transcription of the TGF-beta 2 gene in this model system. To address this possibility, we have examined the activity of the TGF-beta 2 promoter in EC cells and their differentiated cells using gene constructs containing various portions of the TGF-beta 2 promoter inserted upstream of the reporter gene, chloramphenicol acetyltransferase (CAT). We determined that the level of CAT increases approximately ninefold when EC cells were induced to differentiate. Our studies also indicate that the TGF-beta 2 promoter contains at least two positive regulatory elements that are separated by a negative regulatory element. Finally, we have identified a CRE/ATF-like site that appears to be responsible for a positive regulatory element located between -77 and -40.
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PMID:Differential regulation of the transforming growth factor type-beta 2 gene promoter in embryonal carcinoma cells and their differentiated cells. 151 48

We have cloned and sequenced a mouse genomic transforming growth factor beta 1 (TGF-beta 1) DNA fragment that includes the 5' untranslated and regulatory regions of the gene. High-sequence homology with the human TGF-beta 1 gene (66% nucleotide identity in 2.7 kb of DNA upstream of the translational start site) suggested evolutionary conservation of transcriptional regulation for TGF-beta 1. The absence of TATA or CAAT box sequences but the presence of several Sp1-binding and AP-2-like sequences in the promoter region was noted, as previously reported for the human gene. Two transcriptional initiation sites separated by 290 bp were identified by S1 nuclease analysis; these corresponded to transcripts with 866 and 576 nucleotides of 5' untranslated leader sequence. S1 analysis of different mouse tissues indicated that the two transcripts were present in the same ratio even though the total level of TGF-beta 1 mRNA transcripts varied between tissues. Promoter activity adjacent to both transcriptional start sites was demonstrated by using chloramphenicol acetyltransferase fusion genes assayed in mouse AKR-2B fibroblast cells. Transcriptional activation of the promoter by the Ha-ras oncogene was also demonstrated. The minimal promoter constructs (113 and 104 bp 5' of the first and second transcriptional start sites, respectively) were sufficient for induction by Ha-ras. These studies characterize the 5' structure and basal promoter activity of the mouse TGF-beta 1 gene as well as the transcriptional activation of TGF-beta 1 by the Ha-ras oncogene.
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PMID:Characterization of the mouse transforming growth factor-beta 1 promoter and activation by the Ha-ras oncogene. 198 55

Regulation of human type I procollagen gene expression was studied in cultured fibroblasts both at the transcriptional and posttranscriptional level. Transcriptional regulation was examined in cultures transfected with a human pro alpha 2(I) collagen promoter/reporter gene (chloramphenicol acetyltransferase) construct, while posttranscriptional regulation was assessed by parallel determinations of type I procollagen mRNA steady-state levels. Transforming growth factor-beta 1 (TGF-beta 1) elicited a marked, approximately 5-23-fold, enhancement of pro alpha 2(I) collagen promoter activity, which was accompanied by an elevation of type I procollagen mRNA levels. This enhancement of gene expression was suppressed by tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), as determined at mRNA steady-state level, but two distinct mechanisms were involved. TNF-alpha suppressed the pro alpha 2(I) collagen promoter activity, whereas IFN-gamma had only a minimal effect at transcriptional level. The effects of TNF-alpha and IFN-gamma were synergistic, suggesting that combination of these two factors may potentially provide pharmacologic means to counteract tissue deposition of collagen in diseases involving TGF-beta.
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PMID:Tumor necrosis factor-alpha and interferon-gamma suppress the activation of human type I collagen gene expression by transforming growth factor-beta 1. Evidence for two distinct mechanisms of inhibition at the transcriptional and posttranscriptional levels. 212 79

Transforming growth factor-beta 1 (TGF-beta 1) markedly increased the mRNA encoding nerve growth factor (NGF) in cultured rat astrocytes in a time- and concentration-dependent manner. The maximal effect of TGF-beta 1 (a 50-fold increase in NGF-mRNA) was reached after 24 h incubation. The TGF-beta-mediated increase in NGF-mRNA results from enhanced transcription as shown in nuclear run-on studies and in transfection assays using the NGF promoter linked to a chloramphenicol acetyltransferase (CAT) reporter gene. TGF-beta 1 also increased its own expression in astrocytes as well as that of the proto-oncogene c-fos. Intraventricular injection of TGF-beta 1 resulted in an increase of NGF-mRNA levels in the rat hippocampus (3-4 fold) showing that TGF-beta 1 is also effective in increasing NGF expression in vivo.
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PMID:Transforming growth factor-beta 1 stimulates expression of nerve growth factor in the rat CNS. 212 62

Transforming growth factor beta 3 (TGF-beta 3) has been cloned from humans, chickens, pigs, and mice. Although the specific in vivo roles of this form of TGF-beta are unknown, the pattern of embryonic and tissue-specific expression of TGF-beta 3 suggests that it is involved in embryogenesis and cell differentiation. We have cloned and sequenced the TGF-beta 3 5'-flanking region to study the transcriptional regulation of this gene. Characterization of the 5'-flanking region showed a 1104-base pair 5'-untranslated region, a TATA box 21 bp upstream from the transcription start site, and cAMP-responsive element (CRE) and AP-2 binding site consensus sequences starting at 12 and 24 bp, respectively, upstream from the TATA box. Promoter fragments were cloned into a chloramphenicol acetyltransferase reporter plasmid to study functional activity. Basal transcriptional activity of the promoter was regulated by multiple upstream elements including the CRE and the AP-2 site. The CRE was important for both basal and forskolin induction of promoter activity. The TGF-beta 3 promoter was found to be strikingly dissimilar to the TGF-beta 1 promoter. Since the TGF-beta s have activity in promoting or inhibiting proliferation and differentiation of multiple cell types, it seems likely that the differential and tissue-specific transcriptional regulation of these genes is of fundamental importance in the induction and maintenance of differentiated cell types in various tissues.
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PMID:Structural and functional characterization of the transforming growth factor beta 3 promoter. A cAMP-responsive element regulates basal and induced transcription. 214 70

Transforming growth factor beta 1 (TGF-beta 1) is a potent growth inhibitor for many cell types, including most epithelial cells. However, the mechanism of growth inhibition is unknown. In skin keratinocytes, TGF-beta 1 has been shown to inhibit growth and to rapidly reduce c-myc expression. It has been demonstrated that protein synthesis is required for TGF-beta 1 regulation of c-myc in keratinocytes. Here we present evidence that treatment of mouse BALB/MK keratinocyte cells with either antisense c-myc oligonucleotides or TGF-beta 1 inhibited cell entry into S phase. These results suggest that TGF-beta inhibition of c-myc expression may be essential for growth inhibition by TGF-beta 1. The block in c-myc expression by TGF-beta 1 occurred at the level of transcriptional initiation. Studies with a series of 5' deletion c-myc/chloramphenicol acetyltransferase constructs indicated that a cis regulatory element(s), which resides between positions -100 and +71 relative to P1 transcription start site, is responsible for the TGF-beta 1 responsiveness. Based on these data, it is proposed that the mechanism of TGF-beta 1 growth inhibition involves synthesis or modification of a protein that may interact with a specific element(s) in the 5' regulatory region of the c-myc gene, resulting in inhibition of transcriptional initiation.
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PMID:Transforming growth factor beta 1 suppression of c-myc gene transcription: role in inhibition of keratinocyte proliferation. 218 92

A nontransformed rat clonal cell line (UMR-201) with phenotypic characteristics of osteoblastic precursor cells was found to respond to insulinlike growth factor 1 (IGF-1) by increased osteonectin and pro-alpha 1(I)-collagen mRNA expression. Cells were treated for 24 h with insulin, growth hormone, or IGF-1 to study the regulation of messenger RNA for osteonectin and pro-alpha 1(I)-collagen using Northern blot hybridization. UMR-201 cells possess specific high-affinity receptors for growth hormone, although there were no significant effects of growth hormone (10(-9)-10(-7) M) or insulin (10(-9)-10(-6) M) on mRNA species for osteonectin or pro-alpha 1(I)-collagen. However, IGF-1 increased both mRNA species from a concentration of 10(-9) M. The effect on osteonectin mRNA expression was likely due to increased transcription; when 5' flanking osteonectin (ON) genomic fragments were linked to the bacterial reporter gene chloramphenicol acetyltransferase (CAT) and introduced by transfection into UMR-201 cells, the transcriptional activity of the ON-CAT construct was increased 235 and 270% by 10(-8) and 10(-7) M IGF-1, respectively. In contrast, growth hormone did not change the transcriptional activity of the ON-CAT construct. In confirmation of other work, transforming growth factor beta (TGF-beta, 0.1-2.5 ng/ml) increased mRNA for osteonectin and pro-alpha 1(I)-collagen in a dose-dependent manner. Transforming growth factor alpha (TGF-alpha) at 0.1-10 ng/ml had no consistent effects in repeated experiments on osteonectin and pro-alpha 1(I)-collagen mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulinlike growth factor 1 regulates mRNA levels of osteonectin and pro-alpha 1(I)-collagen in clonal preosteoblastic calvarial cells. 220 53

A combined approach of cDNA cloning and direct oligonucleotide mapping of TGF-beta 1 mRNA from several human cell lines has revealed that the major human TGF-beta 1 transcript is 381 bases shorter than originally reported, and that the reduced mRNA size is due to polyadenylation from an ATTAAA signal at position 2136 rather than use of the expected AATAAA signal at position 2517. Moreover, there is no evidence for a significant amount of structural heterogeneity, as a result of alternative polyadenylation, in the human TGF-beta 1 transcripts. Considering that the 381-base domain is not part of the major human TGF-beta 1 mRNA, we analyzed this sequence for potential transcriptional regulatory elements. We have identified a 16-base pair domain which contains three putative phorbol ester responsive elements (TREs) based on homology to the TRE consensus sequence. We also show that this 16-base pair fragment confers phorbol ester responsiveness to the chloramphenicol acetyltransferase gene after transient transfection of the heterologous construct in NIH-3T3 cells. The identification of a TRE immediately downstream of the last TGF-beta 1 exon suggests that a 3' enhancer may play an important role in human TGF-beta 1 gene transcription, and suggests a basis for growth factor-mediated regulation of TGF-beta 1 expression by activation of protein kinase C.
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PMID:Type beta 1 transforming growth factor gene expression. A corrected mRNA structure reveals a downstream phorbol ester responsive element in human cells. 229 44


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