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)

Human CR2 has a restricted cellular distribution, being expressed on B lymphocytes, dendritic cells of the spleen, pharyngeal epithelial cells, and at low levels on some T lymphocytes. CR2 is expressed by mature B lymphocytes, but not by pre-B cells or by plasma cells, suggesting that mechanisms exist for positive and negative regulation of CR2 gene expression during B cell development. S1 nuclease digestion and primer extension analysis positioned the transcriptional start site between 92 and 94 bp upstream of the ATG codon. Nucleotide sequence analysis identified several sequences within the CR2 promoter region with homology to other known promoter sequences. These included a site similar to an AP-1 site, a sequence with 10 of 13 nucleotides identical to the X box of class II genes, and a TATA box. Genomic DNA starting immediately 5' of the sequence encoding the CR2 signal peptide was subcloned upstream of the bacterial chloramphenicol acetyltransferase gene for analysis of functional promoter and enhancer sites. The functional boundaries of the CR2 promoter were determined by deletion analysis, with both the X box-like sequences and the TATA box required for CR2 expression. This analysis revealed sequences with regulatory effects on CR2 gene expression, however, these transcriptional controlling sequences did not act in a tissue specific fashion.
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PMID:Identification of 5'-regions affecting the expression of the human CR2 gene. 183 54

Collagenase, the only enzyme active at neutral pH that initiates collagen degradation, is a major gene product of fibroblasts that have been stimulated with a variety of agents, including phorbol esters. To study mechanisms controlling collagenase gene expression, we transiently transfected rabbit synovial fibroblasts with chimeric constructs containing up to 1.2 kb of the rabbit collagenase 5'-flanking DNA linked to the chloramphenicol acetyltransferase gene (CAT). Our data indicate that the magnitude of the phorbol response is directly linked to the size of the promoter fragment and that the smallest piece of promoter DNA conferring phorbol inducibility is 127 bp. Deletional and mutational analysis of this fragment revealed that the AP-1 sequence alone is insufficient for phorbol inducibility and the presence of at least two additional sequences (a PEA3-like element and a sequence that includes 5'-TTCA-3') is required. In addition, a substantial increase in responsiveness is seen when a fragment containing 182 bp of 5'-flanking DNA is transfected, implicating a 36 bp region located between -182 and -149 as an enhancer. We conclude (1) that the AP-1 sequence is necessary but insufficient for expression of collagenase in adult fibroblasts, (2) that phorbol inducibility depends on cooperation among several sequence elements within the collagenase promoter, and (3) that regulation of this promoter is more complex than previously described.
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PMID:The AP-1 sequence is necessary but not sufficient for phorbol induction of collagenase in fibroblasts. 185 Jun 29

Granulocyte-macrophage colony stimulating factor (GM-CSF) stimulates the growth and differentiation of human hematopoietic progenitor cells by activating transcription of specific genes. The mechanism by which binding of GM-CSF to its receptor stimulates gene expression remains unknown. To examine this process in more detail, we have transfected human monocytic leukemia cells U937 with a plasmid containing an AP-1 enhancer element and a chloramphenicol acetyltransferase recorder gene and treated them with GM-CSF. We find that GM-CSF stimulates a 2-3-fold increase in chloramphenicol acetyltransferase activity over a concentration range 1-1,000 units/ml. Northern and Western blot analysis demonstrates that the mechanism by which GM-CSF stimulates AP-1 enhancer activity involves increases in c-jun and c-fos mRNA levels, and increases in Jun protein. In a similar fashion the treatment of normal human monocytes with GM-CSF also induced increases in total cellular c-jun. Because protein kinase C plays a crucial role in activating c-jun transcription we examined the role of this enzyme in mediating the effects of GM-CSF. Treatment of U937 cells with inhibitors of protein kinase C including staurosporine 10 nM and H-7 50 microM, or down-regulation of protein kinase C by phorbol ester pretreatment blocks the induction of c-jun by GM-CSF. However, HA which does not block protein kinase C had no effect on GM-CSF stimulation of c-jun RNA levels. In addition, GM-CSF treatment causes the rapid translocation of protein kinase C to the particulate fraction which was maximal by 5 min and returned to base line by 80 min. These data suggest that the binding of GM-CSF to its receptor stimulates increases in c-jun mRNA and protein and activates AP-1 enhancer activity. These effects may be at least in part mediated by activation of protein kinase C.
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PMID:Regulation of c-jun expression and AP-1 enhancer activity by granulocyte-macrophage colony-stimulating factor. 190 Aug 39

We demonstrate that a member of the fos family, the fosB gene, gives rise to two transcripts by alternative splicing of exon 4, generating two proteins, FosB of 338 amino acids and a short form, FosB/SF, which contains the DNA binding and dimerization domains but not the 101 amino acids of the C terminus. FosB/SF activates an AP-1-chloramphenicol acetyltransferase construct in NIH 3T3 cells, as determined by transient and stable transfections, although more weakly than does FosB. In contrast to FosB, FosB/SF has lost its ability to repress the dyad symmetry element of the c-fos gene. FosB/SF when expressed in excess to FosB can downmodulate the activity of FosB. Constitutive expression of high levels of FosB/SF in NIH 3T3 cells has no significant inhibitory effect in the induction of cell proliferation or cell cycle progression, indicating that FosB/SF is not a negative regulator of cell growth. This conclusion is further confirmed by the observation that the majority of the Jun molecules are complexed with FosB/SF in the FosB/SF-overexpressing cells.
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PMID:Both products of the fosB gene, FosB and its short form, FosB/SF, are transcriptional activators in fibroblasts. 192 60

Previous studies have shown that treatment of human myeloid leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with induction of monocytic differentiation and expression of the c-jun and c-fos early response genes. The present work demonstrates that the glucocorticoid dexamethasone inhibits TPA-induced increases in c-jun and c-fos mRNA levels in U-937 leukemia cells. These findings were associated with a block in appearance of the monocytic phenotype, including inhibition of TPA-induced increases in lamin A, lamin C, and vimentin transcripts. Other studies have demonstrated that TPA-induced monocytic differentiation and expression of the c-jun and c-fos genes in myeloid leukemia cells are regulated by protein kinase C (PKC). The finding that dexamethasone has no effect on TPA-induced activation of PKC suggests that this glucocorticoid inhibits signals downstream or parallel to this enzyme. Nuclear run-on assays demonstrate that: (1) induction of c-jun and c-fos expression by TPA is regulated by transcriptional mechanisms, (2) TPA-induced expression of c-jun and c-fos does not require protein synthesis, and (3) TPA-induced expression of both genes is inhibited at the transcriptional level by dexamethasone. To further define the effects of dexamethasone at the molecular level, we prepared a series of deleted c-jun promoter fragments linked to the chloramphenicol acetyltransferase (CAT) gene. Increases in CAT activity during transient expression of these constructs in TPA-treated U-937 cells could be assigned to the region (-97 to -20) of the promoter that contains the AP-1 binding site. This induction of CAT activity was sensitive to dexamethasone. These findings suggest that dexamethasone down-regulates TPA-induced transcription of the c-jun gene during monocytic differentiation by inhibiting activation of the AP-1 site.
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PMID:Inhibition of phorbol ester-induced monocytic differentiation by dexamethasone is associated with down-regulation of c-fos and c-jun (AP-1). 193 41

The molecular basis for adipocyte-specific gene expression is not known. We have demonstrated that while short (-168) segments of the 5'-flanking sequence of the adipocyte P2 gene containing AP-1- and C/EBP-binding sites can direct expression of a heterologous gene in cultured adipocytes, they cannot support tissue-specific expression in a transgenic mouse. We have therefore analyzed larger segments of the aP2 5'-flanking region by transfection into adipocytes and have found an enhancer at -5.4 kb. This 500-bp enhancer directs expression of the bacterial chloramphenicol acetyltransferase (CAT) gene in a differentiation-dependent fashion when linked to its own minimal promoter or to an enhancerless SV40 promoter. Moreover, this enhancer stimulates very strong and highly specific expression from the CAT gene in the adipose tissues of transgenic mice. A smaller fragment (190 bp) having enhancer activity in adipocytes was defined and demonstrated to contain a binding site for an abundant nuclear protein. This factor has the binding specificity and several other properties characteristic of the nuclear factor 1 (NF-1) transcription/replication factor family, and mutation of this NF-1-binding site greatly reduces the function of the 500-bp enhancer. These results identify and characterize the first functional enhancer with specificity for adipose cells and also demonstrate that a member(s) of the NF-1 family is involved in adipocyte-specific gene expression.
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PMID:Identification of a potent adipocyte-specific enhancer: involvement of an NF-1-like factor. 200 42

Cultured neonatal rat cardiac myocytes express at least three isozymes of protein kinase C (PKC), and two PKC isozymes are translocated to different intracellular sites on activation with alpha 1-adrenergic agonists or phorbol myristate acetate. Differential intracellular localization upon activation was compatible with differential function, and we therefore asked whether PKC isozymes had distinct roles in regulating transcription of the cardiac myosin heavy chain (MHC) genes. Cardiac myocytes were transfected with chloramphenicol acetyltransferase reporter plasmids containing the promoters of the beta-MHC or alpha-MHC isogenes. An alpha 1-adrenergic agonist stimulated the beta-MHC promoter by 3-fold but had no effect on the alpha-MHC promoter. This pattern of MHC promoter regulation by an alpha 1 agonist was the same as that found previously for the endogenous MHC mRNAs in this model system. Myocytes were then co-transfected with the beta- or alpha-MHC-chloramphenicol acetyltransferase plasmids and expression plasmids encoding wild-type or constitutively activated mutants of the alpha- and beta-isozymes of PKC. Co-transfection with wild-type alpha-PKC or wild-type beta-PKC did not stimulate the beta-MHC promoter, and none of the expressed PKCs affected the alpha-MHC promoter. However, the constitutively activated mutant of beta-PKC stimulated the beta-MHC promoter by 8-fold, whereas stimulation by the activated alpha-PKC mutant was only 40% as great (3-fold). In contrast, the constitutively activated alpha-PKC and beta-PKC mutants were equally potent in stimulating a reporter plasmid containing AP-1 recognition sequences. All transfected PKCs were expressed equally in the myocytes, as judged by immunofluorescence. These data indicate that transcription of the beta-MHC isogene is stimulated preferentially by beta-PKC in cardiac myocytes and provide direct evidence for differential functions of alpa-PKC and beta-PKC in transcriptional regulation.
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PMID:Expression of a constitutively activated mutant of the beta-isozyme of protein kinase C in cardiac myocytes stimulates the promoter of the beta-myosin heavy chain isogene. 203 58

To better understand the regulation of interleukin-7 receptor (IL-7R) expression, we have pursued a detailed analysis of the structure of the murine and human IL-7R genes. The genes consist of eight exons, the sizes of which are conserved in mouse and human cells, spread out over 24 kbp (murine) and 19 kbp (human). A differential splicing event results in an mRNA encoding a secreted form of the human IL-7R gene. Primer extension and S1 nuclease analysis show a single transcriptional start site for the murine IL-7R gene. The 5'-flanking region of the murine IL-7R gene contains TATA- and CAAT-like sequences. The promoter region also contains a functional interferon regulatory element, to which the interferon-induced nuclear factors IRF-1 and IRF-2 are capable of binding and which is able to confer interferon-inducible expression on a heterologous gene. There are also potential binding sites for the transcription factors AP-1 and AP-2 as well as multiple glucocorticoid response elements. A fusion gene containing 2.5 kb of murine IL-7R 5' regulatory sequence linked to the bacterial chloramphenicol acetyltransferase gene directed expression of chloramphenicol acetyltransferase activity in murine pre-B-cell line 70Z/3 but not in the mouse fibroblast cell line NIH 3T3. Comparison of the murine and human IL-7R exon/intron boundaries with those of other hematopoietin receptor superfamily members whose exon/intron boundaries are also known reveals a conserved evolutionary structure.
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PMID:Organization of the murine and human interleukin-7 receptor genes: two mRNAs generated by differential splicing and presence of a type I-interferon-inducible promoter. 203 16

Lesion of the sciatic nerve caused a rapid increase in c-fos and c-jun mRNA that was followed about 2 hr later by an increase in nerve growth factor (NGF) mRNA. To evaluate whether the initial increase in c-fos mRNA is causally related to the subsequent increase in NGF mRNA, we performed experiments with fibroblasts of transgenic mice carrying an exogenous c-fos gene under the control of a metallothionein promoter. In primary cultures of these fibroblasts, CdCl2 evoked a rapid increase in exogenous c-fos mRNA, followed immediately by an increase in endogenous c-jun mRNA and with a slight delay by an increase in NGF mRNA. In fibroblasts of C3H control mice, CdCl2 had no effect on the mRNA levels of the protooncogenes c-fos and c-jun or of NGF. Additional evidence for a causal relationship between c-fos induction and the subsequent increase in NGF mRNA was obtained in cotransfection experiments. Fibroblasts of C3H control mice were cotransfected with a metallothionein-promoter-driven c-fos expression vector and a NGF promoter-chloramphenicol acetyltransferase reporter gene construct. Induction of the exogenous c-fos by CdCl2 resulted in increased activity of the NGF promoter. DNase I footprint experiments demonstrated that a binding site for transcription factor AP-1 (Fos/Jun heterodimer) in the first intron of the NGF gene was protected following c-fos induction. That this protected AP-1 site indeed was functional in the regulation of NGF expression was verified by deletion experiments and by a point mutation in the corresponding AP-1 binding region in the NGF promoter-chloramphenicol acetyltransferase reporter construct.
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PMID:Lesion-induced increase in nerve growth factor mRNA is mediated by c-fos. 211 Oct 20

To investigate the transcriptional regulation of human glutathione S-transferase pi (GST pi) gene expression, we fused the GST pi promoter, including 2203 bp of the 5'-flanking region, exon 1, and most of intron 1, to the chloramphenicol acetyltransferase (CAT)-encoding reporter gene (cat). When transfected into human cell lines, this GST-cat construct (-2203 GST-cat) supported high level cat gene expression. RNase-protection and primer-extension experiments showed that the normal GST pi transcriptional start point (tsp) is utilized, and furthermore, that intron 1 is faithfully removed by splicing from the majority of primary GST-cat transcripts. A series of constructs containing deletions in the GST pi sequences of the -2203 GST-cat vector were prepared to define potential regulatory regions. Transfection of these deletion plasmids revealed that a region between GST pi sequences -80 and -8 is absolutely required for cat expression. Furthermore, transfection of the -2203 GST-cat and deletion vectors into two human cell lines--one line which does not produce endogenous GST pi (HeLa cells) and one which produces high levels of endogenous GST pi (HS 578T cells)--failed to identify sequences that differentially influence the level of transcription in either cell line. A putative TRE (TPA responsive element or AP-1 recognition sequence) strategically situated upstream from the GST pi tsp (-69 to -63) was examined by TPA treatment of HeLa cells transfected with GST-cat DNA. Additionally, the potential interaction of fos and jun proteins with the GST pi promoter was examined by co-transfection of GST-cat constructs with jun and fos expression vectors in F9 cells. Both of these treatments, which are known to enhance transcription of several genes containing 5'-flanking TREs, failed to induce GST-cat expression. These data suggest that the putative TRE sequence in GST pi is unresponsive both to phorbol esters and to these particular transcriptional activating factors of the fos and jun family.
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PMID:Regulation of human glutathione S-transferase pi gene transcription: influence of 5'-flanking sequences and trans-activating factors which recognize AP-1-binding sites. 211 5


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