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)

The cMG1 gene was originally identified as a mitogen-stimulated primary response gene. However, in contrast to genes such as c-fos and TIS11, cMG1 is also expressed at significant levels before and after the transient elevation induced by agonists. We have sequenced a 1.3 kb rat genomic cMG1 clone, which includes 931 bp upstream of the transcription start site identified by primer-extension analysis. A 1033 bp fragment, including this 5'-flanking sequence, directed the expression of the reporter gene chloramphenicol acetyltransferase (CAT) in transfected NIH-3T3 cells. Progressive 5'-to-3' deletion indicated that an element located between -138 and -114 was responsible for most of this basal CAT expression. DNA mobility-shift assays showed that the sequence between -143 and -105 contained binding sites for cellular proteins, the principal complexes involving nucleotides between -119 and -105. We conclude that these complexes may represent the transcription factor-DNA element interactions that determine basal cMG1 expression.
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PMID:Identification of a functional promoter element in the 5'-flanking region of the rat cMG1/TIS11b gene. 757 62

Many transformed mouse lung cells, including LM2 cells, contain activating mutations in the Ki-ras gene and show reduced responsiveness to growth inhibition by glucocorticoids. LM2GR cells, which are LM2 cells stably transfected with a rat glucocorticoid receptor (GR) gene, were used to determine whether increasing glucocorticoid responsiveness can influence aspects of the transformed phenotype. LM2GR cells grew slower and had a lower final saturation density than the parental LM2 cells. Expression of growth-related genes was examined by northern blot analysis. The cells were serum-deprived and treated with fetal bovine serum (FBS), steroid-stripped FBS (ssFBS), dexamethasone, or 12-O-tetradecanoylphorbol-13-acetate. The level and pattern of Ki-ras mRNA expression was similar in both LM2 and LM2GR cells, but histone H4 mRNA was expressed in a more regulated fashion in LM2GR cells. The induction of c-jun and c-fos mRNA expression lasted longer in the LM2GR cells treated with ssFBS; however, the maximal induction was greater in the LM2 cells treated with FBS. LM2GR cells demonstrated similar activator protein-1 (AP-1) activity but higher GR activity than LM2 cells as determined by using AP-1-chloramphenicol acetyltransferase (CAT) and mouse mammary tumor virus-CAT transient transfection assays, consistent with the higher level of GR mRNA in LM2GR cells. Both cell lines exhibited the ability to grow in soft agar and to form tumors in nude mice. These results indicate that introduction of a functional GR transgene into LM2 cells can increase glucocorticoid responsiveness and alter the expression of genes involved in growth regulation but cannot overcome anchorage-independent cell growth or tumorigenicity, apparently because of the presence of an activated Ki-ras gene.
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PMID:Effect of increased glucocorticoid responsiveness in transformed mouse lung cells. 761 16

The AP-1 consensus sequences (TGAGTCA) are the major 12-O-tetradecanoylphorbol113-acetate (TPA) responsive elements shared by several TPA inducible genes, such as c-sis, c-fos, c-myc, collagenase, stromelysin, hMTIIA and SV40. However, the role of AP-1 binding sites, which are present in the introns 3, 5, and 11 of ODC gene, in the regulation of TPA-induced ornithine decarboxylase (ODC) gene transcription are unknown. We determined the TPA responsiveness of the AP-1 sequences in the introns of ODC gene in CV-1 cells which induce ODC activity and mRNA in response to TPA treatment. ODC introns containing AP-1 sequences were inserted into the chloramphenicol acetyltransferase (CAT) reporter gene. Transient transfection of CV-1 cells with the intron-CAT constructs followed by TPA treatment did not induce CAT activity. However, when flanking regions of the AP-1 site in intron 3 were narrowed down to 74 bp, TPA induced CAT activity by 5- to 7-fold. The TPA-inducibility could be eliminated by mutation of the AP-1 site (TGAGTCA-->TGATGCCA or TGATGA) in 74 bp of intron 3. These results indicate that the AP-1 sequences in the intact ODC introns may not be responsive to TPA. The flanking sequences of the AP-1 site may be crucial to determine whether the AP-1 site is accessible to the TPA-induced transcriptional factor(s).
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PMID:Lack of 12-O-tetradecanoylphorbol-13-acetate responsiveness of ornithine decarboxylase introns which have AP-1 consensus sequences. 765 80

Ferritin, the major intracellular iron storage protein of eucaryotic cells, is regulated during inflammation and malignancy. We previously reported that transcription of the H subunit of ferritin (ferritin H) is negatively regulated by the adenovirus E1A oncogene in mouse NIH 3T3 fibroblasts (Y. Tsuji, E. Kwak, T. Saika, S. V. Torti, and F. M. Torti, J. Biol. Chem. 268:7270-7275, 1993). To elucidate the mechanism of transcriptional repression of the ferritin H gene by E1A, a series of deletions in the 5' flanking region of the mouse ferritin H gene were constructed, fused to the chloramphenicol acetyltransferase (CAT) gene, and transiently cotransfected into NIH 3T3 cells with an E1A expression plasmid. The results indicate that the E1A-responsive region is located approximately 4.1 kb 5' to the transcription initiation site of the ferritin H gene. Further analyses revealed that a 37-bp region, termed FER-1, is the target of E1A-mediated repression. This region also serves as an enhancer, augmenting ferritin H transcription independently of position and orientation. FER-1 was dissected into two component elements, i.e., a 22-bp dyad symmetry element and a 7-bp AP1-like sequence. Insertion of these DNA sequences into a ferritin H-CAT chimeric gene lacking an E1A-responsive region indicated that (i) the 22-bp dyad symmetry sequence by itself has no enhancer activity, (ii) the AP1-like sequence has moderate enhancer activity which is repressed by E1A, and (iii) the combination of the dyad symmetry element and the AP1-like sequence is required for maximal enhancer activity and repression by E1A. Gel retardation assays and cotransfection experiments with c-fos and c-jun expression vectors suggested that members of the Fos and Jun families bind to the AP1-like element of FER-1 and contribute to its regulation. In addition, gel retardation assays showed that E1A reduces the ability of nuclear proteins to bind to the AP1-like sequence without affecting the levels of nuclear factors that recognize the 22-bp dyad symmetry element. Taken together, these results demonstrate that FER-1 serves as both an enhancer of ferritin H transcription and a target for E1A-mediated repression.
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PMID:FER-1, an enhancer of the ferritin H gene and a target of E1A-mediated transcriptional repression. 765 32

We have analyzed the transcriptional regulation of the fra-2 gene in chicken embryo fibroblasts. Like c-fos, fra-2 was inducible by phorbol ester, cAMP and calcium ionophore, as well as serum. In all three cases, the induction of two species of fra-2 transcript (5.7 kb and 6.8 kb) was delayed and prolonged compared with that of c-fos mRNA. The size difference between the two transcripts was attributable to the heterogeneity of the 3'-end, probably reflecting utilization of different polyadenylation sites. The major transcriptional start point is located at 30 bp downstream of a TATA-like sequence. In the fra-2 promoter region, which is located in a typical CpG island, enhancer consensus sequences such as SCM, SRE, GC boxes and CRE-like sequences were detected upstream of the TATA-like sequence in the same order as that in the 5'-upstream region of the chicken c-fos gene. Fibroblast transfection studies with a series of promoter deletion constructs positioned upstream of bacterial chloramphenicol acetyltransferase indicated, however, that SRE-like sequence is not the sole responsible element for the serum induction, and that a minimal fragment containing no SRE-like sequence is sufficient for this induction. Two typical AP-1 sequences are located between the major transcriptional initiation site and the coding sequence, and the binding activity of protein complexes to these sequences was induced by serum.
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PMID:Analysis of fra-2 gene expression. 768 44

Previous studies suggested that individual components of the activator protein 1 (AP-1) complex behave in a highly idiosyncratic fashion at the level of the human atrial natriuretic peptide (ANP) gene promoter. ANP gene transcription is activated by c-jun and is generally suppressed by c-fos. In the present study, fra-1, a close relative of the c-fos gene product in terms of its structure and functional activity, behaved like fos in cardiac atriocytes, effecting an approximately 50% reduction in c-jun-activatable expression of a human ANP chloramphenicol acetyltransferase (CAT) reporter. In cardiac ventriculocytes, however, fra-1 effected a synergistic amplification of the c-jun response (a 2.5-fold increase over c-jun alone). In atrial cells, fos-like proteins were not uniformly inhibitory in that a carboxy terminal deletion mutant of c-fos activated a human ANP-CAT reporter in the atriocyte cultures. Finally, using a series of domain-swap mutations in the fos/fra structural sequences, we showed that sequences at both the amino and the carboxy termini are required to realize the full fra-1-dependent stimulatory effect as well as the c-fos-dependent inhibition of ANP gene transcription. These findings suggest considerable heterogeneity in the response of the ANP promoter to different components of the AP-1 complex. Such heterogeneity may serve to broaden the range of biological responses available to this promoter as the cardiac cell attempts to adapt to perturbations in the extracellular environment.
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PMID:Fra-1, a Fos gene family member that activates atrial natriuretic peptide gene transcription. 772 15

Transcriptional activation of the mouse c-fos gene by the adenovirus 243-amino-acid E1A protein requires a binding site for transcription factor YY1 located at -54 of the c-fos promoter. YY1 normally represses transcription of c-fos, and this repression depends on the presence of a cyclic AMP (cAMP) response element located immediately upstream of the -54 YY1 DNA-binding site. This finding suggested that the mechanism of transcriptional repression by YY1 might involve a direct interaction with members of the ATF/CREB family of transcription factors. In vitro and in vivo binding assays were used to demonstrate that YY1 can interact with ATF/CREB proteins, including CREB, ATF-2, ATFa1, ATFa2, and ATFa3. Structure-function analyses of YY1 and ATFa2 revealed that the C-terminal zinc finger domain of YY1 is necessary and sufficient for binding to ATFa2 and that the basic-leucine zipper region of ATFa2 is necessary and sufficient for binding to YY1. Overexpression of YY1 in HeLa cells resulted in repression of a mutant c-fos chloramphenicol acetyltransferase reporter that lacked binding sites for YY1, suggesting that repression can be triggered through protein-protein interactions with ATF/CREB family members. Consistent with this finding, repression was relieved upon removal of the upstream cAMP response element. These data support a model in which YY1 binds simultaneously to its own DNA-binding site in the c-fos promoter and also to adjacent DNA-bound ATF/CREB proteins in order to effect repression. They further suggest that the ATF/CREB-YY1 complex serves as a target for the adenovirus 243-amino-acid E1A protein.
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PMID:Transcriptional repression of the c-fos gene by YY1 is mediated by a direct interaction with ATF/CREB. 776 93

A mesenchymal-epithelial cell interaction exists in the testis between the Sertoli cells that form the seminiferous tubule and the mesenchymal-derived peritubular myoid cells that surround the tubule. Analysis of the mesenchymal-epithelial interactions between these cells revealed the local production of a mesenchymal factor, PModS. PModS modulates the differentiated functions of Sertoli cells in vitro, including stimulation of the iron-binding protein transferrin (Tf). Previous results have indicated that PModS-induced Tf gene expression involves the activation of immediate early genes. One of the immediate early genes was identified as c-fos. The importance of c-fos was demonstrated in the current study when a c-fos antisense oligonucleotide was found to inhibit the ability of PModS to induce the expression of a Tf promoter-chloramphenicol acetyltransferase (CAT) construct. The regulation of c-fos by PModS was investigated with various CAT constructs containing segments of the c-fos promoter, such as the serum response element (SRE), sis-inducible element (SIE), cAMP response element (CRE), and phorbol ester/TPA response element (TRE), transfected into cultured Sertoli cells. PModS has no effect on cAMP response element-CAT or TRE-CAT, suggesting that PModS does not act through stimulation of cAMP and protein kinase C pathways. PModS was found to activate the c-fos SRE-CAT construct and the SIE-CAT construct. A construct containing both SIE and SRE was stimulated to the same degree as either element alone. Gel mobility shift assays using nuclear extracts from PModS-stimulated Sertoli cells and a radiolabeled SRE oligonucleotide resulted in retarded mobility of a DNA-protein complex. A gel shift with a SRE oligonucleotide containing an ETS domain resulted in a unique shift only detected in PModS stimulated cells. PModS also promoted a gel shift with the SIE that is adjacent to the SRE on the c-fos promoter. The data imply that PModS can activate the c-fos promoter through the SRE and SIE. PModS caused a labeled activating protein 1 (AP1) oligonucleotide to form a DNA-protein complex, indicating activation of the c-fos gene and binding of the c-fos/jun complex. To study the downstream regulation of Sertoli cell differentiation, Tf gene expression was examined. CAT constructs containing deletion mutants of a 3-kilobase (kb) mouse Tf promoter were used. When transfected into Sertoli cells the 581-base pair Tf minimal promoter had only a slight response to PModS, but was activated by FSH. The 2.6-kb Tf promoter construct responded to PModS.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of specific response elements of the c-fos promoter and involvement of intermediate transcription factor(s) in the induction of Sertoli cell differentiation (transferrin promoter activation) by the testicular paracrine factor PModS. 778 31

The functional induction of c-fos in the sodium butyrate-induced differentiation of F-98 glioma cells was studied. Fos protein level was increased by butyrate. In contrast, c-Jun protein was constitutively expressed and was not affected by butyrate. Gel-retardation assay indicates Fos as a component of the complex formed between the consensus oligonucleotide of the TPA (PMA, phorbol 12-myristate 13-acetate) response element (TRE) and nuclear extract prepared from butyrate-treated cells. Transfection studies showed that butyrate increased transcription from a multimeric TRE-driven reporter construct, and the effect was mimicked by transfecting cells with fos-expression plasmid. Furthermore, under conditions of c-fos over-expression, transactivation by butyrate was essentially abolished. These data suggest that Fos induction had a functional role in gene activation. Characterization of stable c-fos transfectants demonstrated that these cells displayed alterations in morphology, showed serum-dependent growth, had slower growth rates and grew to lower saturation densities than did untransfected F-98 cells or transfected cells that did not express c-fos. Immunofluorescent staining indicated that fos transfectants also had elevated glial fibrillary acidic protein ('GFAP') expression. Transfection of the c-fos promoter-chloramphenicol acetyltransferase fusion gene into F-98 cells revealed that activation of c-fos by butyrate was exerted at the promoter level, and sequences located within nucleotides -757 to -402 of the c-fos promoter were responsible for butyrate induction. Our data indicate that transcriptional activation of c-fos through its promoter by butyrate resulted in increased Fos protein expression. Transfection studies show that both c-fos and butyrate activate TRE-containing genes, and fos may be a downstream mediator of butyrate. Furthermore, expression of c-fos plays a major role in modulating the growth properties of F-98 cells.
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PMID:Analysis of c-fos expression in the butyrate-induced F-98 glioma cell differentiation. 786 28

The mechanism by which transforming Ha-ras induces c-fos expression in HC11 mouse mammary epithelial cells was investigated with regard to controversial data concerning the role of protein kinase C (PKC) and the required promoter elements of the fos gene. HC11 cells carrying a glucocorticoid-inducible Ha-ras (val12) construct were transfected with a chloramphenicol acetyltransferase (CAT) reporter gene under the control of a human fos promoter which includes the serum response element (SRE), the adjacent c-fos AP-1 site (FAP) and the cAMP response element (CRE). Induction of the Ha-ras gene by dexamethasone lead to a transactivation of expression of the transfected fos promoter construct which was inhibited by the PKC inhibitor BM41440 and abrogated in PKC-'depleted' cells. A similar transactivation was observed when the fos promoter construct was co-transfected with a constitutively active ras expression vector. Again, this effect was depressed by the PKC inhibitor and abolished in PKC-'depleted' cells. 'PKC-depletion' was achieved by long-term exposure to 12-O-tetradecanoylphorbol-13-acetate. This procedure was shown to deplete cells of PKC alpha and to reduce significantly PKC epsilon. Long-term exposure to bryostatin 1 selectively depletes PKC alpha. Depletion of PKC alpha by bryostatin 1 does not reduce the transcriptional activation of the SRE-FAP-TK-CAT (TK: thymidine kinase) construct by Ha-ras. In order to delineate the promoter elements mediating the transcriptional activation, constructs which lack the FAP and the CRE sites but contain an intact SRE were co-transfected with the ras construct. Elimination of the FAP and CRE sequences did not affect the transcriptional activation by Ha-ras (val12). It is concluded that in HC11 cells, transforming Ha-ras activates c-fos expression in a PKC-dependent manner, presumably implying PKC epsilon, and that the SRE is sufficient to mediate transcriptional activation.
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PMID:Activation of c-fos expression by transforming Ha-ras in HC11 mouse mammary epithelial cells is PKC-dependent and mediated by the serum response element. 791 86


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