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)

In recent studies we have identified PC2 and PC3, members of a family of serine proteases that are related structurally to subtilisin, and have provided evidence that these are involved in the tissue-specific processing of prohormones and neuropeptides. PC2 is expressed at high levels in the islets of Langerhans, where it participates in the processing of proinsulin to insulin (S.P.S. and D.F.S., unpublished data). To evaluate the regulated expression of the human PC2 (hPC2) gene we have analyzed its structure and characterized its promoter. A map of the gene was constructed by using 11 clones isolated from two human genomic DNA libraries. The gene spans greater than 130 kilobase pairs and consists of 12 exons. Comparison with the structure of the gene encoding human furin, another member of this superfamily, revealed a high degree of conservation of exon-intron junctions. The hPC2 gene was localized to chromosome 20, band p11.2. The 5' flanking region of the hPC2 gene is very G+C-rich and contains six potential Sp1 binding sites but no TATA or CAAT box. Expression of chloramphenicol acetyltransferase reporter fusions containing the putative promoter region was observed to occur in beta TC-3 mouse insulinoma cells but not in HepG2 human hepatoma cells, consistent with the known tissue-specific pattern of expression of the hPC2 gene. Analysis of the level of chloramphenicol acetyltransferase activity with several deletion mutants identified the region from -1100 to -539 from the translation start site as essential for hPC2 promoter activity.
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PMID:Identification and analysis of the gene encoding human PC2, a prohormone convertase expressed in neuroendocrine tissues. 159 2

We have detected a common (allele frequency 0.53/0.47) single base pair insertion/deletion polymorphism 675 base pairs upstream from the start of transcription of the plasminogen activator inhibitor-1 (PAI-1) gene, using the chemical cleavage mismatch analysis. "Band shift assays" suggest that the allele with the single base pair insertion contains an additional protein binding site which is not present in the del allele. Competition experiments confirmed that the binding was specific to the sequence of the ins allele and suggest that proteins bound to this site may be NF-kB-like proteins. Analysis of chloramphenicol acetyltransferase (CAT) mRNA produced by constructs containing the PAI-1 promoter (-805 to +83) showed that the deletion allele produced six times more mRNA than the insertion allele in response to interleukin-1 (p < 0.001). In a sample of 107 young patients with previous myocardial infarction and 95 healthy population-based subjects, the del allele was associated with increased PAI-1 levels, 21% higher than the sample mean in the del homozygotes (p < 0.05). This study also suggested that individuals homozygous for the del allele may have an altered response to the acute phase stimulus. Taken together these results suggest that the insertion/deletion polymorphism in the PAI-1 promoter is of functional importance in regulating the expression of the PAI-1 gene.
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PMID:The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. 838 72