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)

Retinoic acid (RA) and epidermal growth factor (EGF) regulate growth and differentiation of epithelial cells. RA has both direct and indirect effects on gene expression. Direct effects result from modulation of the transcriptional activity of genes, which contain RA response elements (RARE) recognized by trans-acting nuclear RA receptors (RARs). A second indirect mechanism for the modulatory effects of RA is by the induction or repression of growth factors and growth factor receptors. There is evidence for functional interactions between RA and the EGF receptor (EGFR). RA enhances the proliferative response of cultured keratinocytes to EGF, increases the number of EGFRs on the surface of some cells, and induces EGFR promoter activity in most cells. In contrast, immunoprecipitation, Northern blot, and nuclear run-on analysis described in this paper show that RA suppresses EGFR synthesis at the transcriptional level in human epidermoid carcinoma ME180 cells. Deletion analysis of EGFR gene promoter mutants linked to the chloramphenicol acetyltransferase gene revealed the existence of a region of the promoter, -771 to -384, which is responsive to RA. Gel retardation data indicated that a cell-type nuclear protein which binds to this novel element is suppressed by RA in a dose-dependent manner. This decrease coincides with a decreased steady-state level of RAR-gamma mRNA. These data strongly suggest that the EGFR promoter is regulated by RAR-gamma, which itself is under the control of RA. Other cell-specific trans-acting factors may be involved in this regulation.
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PMID:Transcriptional control of epidermal growth factor receptor by retinoic acid. 151 68

The retinoic acid (RA)-associated differentiation of murine F9 teratocarcinoma stem cells results in dramatic changes in gene expression. The cellular gene encoding the B1 subunit of the extracellular matrix protein laminin is transcriptionally activated by RA, and its transcription is further enhanced by N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate (Bt2cAMP) during the differentiation of F9 stem cells into extraembryonic parietal endoderm cells. We now report that expression vectors encoding the human RA receptors RAR-alpha, RAR-beta, and RAR-gamma can activate chloramphenicol acetyltransferase (CAT) expression from laminin B1 promoter/CAT expression vectors (e.g., p1.6LAMCAT) in RA-treated F9 cells, as measured in a transient transfection assay. Bt2cAMP does not further enhance the RA-associated increase in CAT activity. Through the use of deletion and mutation analyses, the RA-responsive element (RARE) of the murine laminin B1 gene has been defined as a 46-base-pair element between -477 and -432 of the laminin B1 5' flanking region. Insertion of a region of DNA containing this RARE in either orientation into a thymidine kinase promoter/CAT expression vector causes CAT expression to be activated 5- to 9-fold by the cotransfected human RAR-alpha or RAR-beta constructs in RA-treated F9 cells, and this RARE also functions in human HeLa cells. In contrast, this RARE in the p1.6LAMCAT vector does not activate CAT expression when cotransfected into F9 stem cells with the c-erbA gene in the presence of thyroid hormone. This suggests that the laminin B1 gene is activated by RA but not by thyroid hormone in vivo.
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PMID:A retinoic acid-responsive element is present in the 5' flanking region of the laminin B1 gene. 255 99

The current study was undertaken to determine the mechanism by which the retinoid all-trans-retinoic acid regulates pro alpha1(I) collagen gene expression in fetal rat skin fibroblasts. FRS fibroblasts were stably transfected with the ColCat3.6 plasmid, which contains a portion of the 5' flanking region of the rat pro alpha1(I) collagen gene linked to a reporter gene, chloramphenicol acetyltransferase. The effect of t-RA on CAT activity was determined as a function of concentration and incubation time. Maximal inhibition of CAT activity by t-RA occurred at 10(-8) M after 48 h of treatment. Transforming growth factor-beta1 did not block the inhibitory effect of t-RA on CAT activity. Computer sequence analysis of the 3.6-kb DNA fragment that contains the promoter for the rat pro alpha1(I) collagen gene identified a direct repeat RARE sequence composed of one diverse (5'-AGTAGA-3') and one idealized (5'-GGGTCA-3') half site located at positions -1345 and -1335, respectively. Two nuclear retinoid receptors that were expressed in bacteria, retinoic acid receptor-gamma and retinoid X receptor-alpha, were found to bind specifically to a double-stranded oligonucleotide containing the RARE in gel mobility shift assays. Mutation of the idealized half-site eliminated the binding of receptor proteins to the oligonucleotide. Gel mobility shift assays using nuclear protein extracts prepared from t-RA-treated FRS fibroblasts showed that binding to the oligonucleotide containing the RARE was decreased from control values. The same assays performed with the mutated oligonucleotide resulted in only slight binding. These studies indicate that t-RA downregulates the promoter activity of the rat pro alpha1(I) collagen gene by decreasing the binding of nuclear protein to the RARE sequence in the 5' flanking region of the gene.
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PMID:All-trans-retinoic acid inhibition of Pro alpha1(I) collagen gene expression in fetal rat skin fibroblasts: identification of a retinoic acid response element in the Pro alpha1(I) collagen gene. 907 77