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)

We isolated and characterized four forms of rat CYP11B genes, which were tentatively named CYP11B1, -B2, -B3, and -B4. Genomic Southern analyses indicated that the members of the rat CYP11B gene subfamily were confined to these four genes; among them, CYP11B1 and -B2 encoded steroid 11 beta-hydroxylase and aldosterone synthase, respectively, while CYP11B3 was a gene highly homologous to CYP11B1 without a known expression product. By being devoid of a region spanning two exons conserved in the other three, CYP11B4 was presumably a pseudogene. In the nucleotide sequences, CYP11B1, -B3, and -B4 showed 95-96 and 93-100% identities in the coding and 0.5-kilobase 5'-flanking regions, respectively. However, the homology between the nucleotide sequences of one of the three and CYP11B2 was rather low, about 90 and 50% in the coding and 0.5-kilobase 5'-flanking regions, respectively. As a whole, CYP11B2 rather than CYP11B1, -B3, or -B4 was more homologous to CYP11B genes of other animals such as cow and human. In transient transfection experiments using mouse adrenocortical Y1 cells and chloramphenicol acetyltransferase gene constructs, the 0.5-kilobase 5'-flanking region of CYP11B1 had a 4- and 10-fold higher promoter activity than the corresponding regions of CYP11B2 and -B3, respectively. The possible presence of a suppressive element(s) was noted in the upstream of the 0.5-kilobase region of CYP11B1. Although a variant of cAMP-responsive element, which was present in rat CYP11B2 and all known CYP11B genes of other animals, was modified in rat CYP11B1 and -B3 genes, dibutyryl cAMP stimulated all the promoter activities of the 5'-flanking regions of the rat genes by 3-fold.
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PMID:Isolation and characterization of rat CYP11B genes involved in late steps of mineralo- and glucocorticoid syntheses. 847 52

We studied the regulation of the hamster CYP11B2 gene in the NCI-H295 cell line, which is known to produce aldosterone in response to stimulation by angiotensin II (AII) and KCl. Ten deletion plasmids harboring the 5'-untranslated region of the CYP11B2 gene were used for chloramphenicol acetyltransferase (CAT) assays. Transient transfections showed progressively increasing basal promoter activity by constructs beyond the TATA box, with a peak occurring with the -167 bp construct which contains putative Adl, Ad2, Ad5 and the newly reported -143/-161 cis-element sequences. The promoter activity was lower with the construct containing the putative Ad3 cis-element and increased with longer constructs. This indicates the presence of both inhibitory and stimulatory cis-elements in this area of the gene. Expression of the reporter gene of all constructs was stimulated by AII and KCl, with the exception of the construct containing only the TATA box, which showed 6-fold and 10-fold increases occurring with the -167 bp deletion plasmid. The patterns of increase in CAT activity with AII and KCI treatment were similar, showing that these two regulators can stimulate hamster CYP11B2 promoter activity through common cis-elements. The calcium channel antagonist nifedipine blocked the stimulatory effects of KCl on CAT activity, showing the involvement of calcium channels in the regulation of CYP11B2 gene transcription by KCl. 12-O-Tetradecanoylphorbol 13-acetate, a known stimulator of the protein kinase C (PKC) signaling pathway, was without significant effect on CAT activity. Bisindolylmaleimide, a specific inhibitor of PKC, had a significant enhancing effect (3.4- to 6-fold), indicating that PKC may negatively regulate the expression of the hamster CYP11B2 gene in NCI-H295 cells. A mutation was induced in the sequence -143/-161 of the - 350 bp construct in order to determine its importance in the regulation of hamster CYP11B2 promoter activity. The stimulatory effects of AII, KCl, forskolin and bisindolylmaleimide on CAT activity were significantly less in the mutant than in the wild type. These results confirm that this cis-element is necessary in maintaining a high level of transcriptional activity in stimulated NCI-295H cells. In conclusion, using NCI-295H transfected cells, we have found that the 5'-untranslated region of the hamster CYP11B2 gene possesses transcriptional activity with stimulatory and also inhibitory cis-elements; CYP11B2 promoter activity can be stimulated by AII, KCl, forskolin, dibutyryl cAMP and bisindolylmaleimide. Our results suggest that this gene is positively regulated through the protein kinase A signaling pathway and through calcium channels, whereas PKC may have a negative regulatory effect upon the transcription of the CYP11B2 gene. Furthermore, we have shown that the cis-element -143/-161 in the 5'-untranslated region of the hamster CYP11B2 gene is important in maintaining a high level of promoter activity in stimulated NCI-295H cells.
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PMID:Transcriptional activity of the hamster CYP11B2 promoter in NCI-H295 cells stimulated by angiotensin II, potassium, forskolin and bisindolylmaleimide. 958 33