Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1332347 (ADH)
 2,230 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 5'-flanking region of the human gene encoding beta-alcohol dehydrogenase (ADH2) was shown by DNase I footprinting to contain three tandem binding sites for purified glucocorticoid receptor. The three binding sites lie very close together between nucleotide (nt) positions -245 and -171 with respect to the transcription start point. DNase I footprinting using a rat liver nuclear extract indicated a lack of protection of the glucocorticoid receptor binding sites, but protection of a sequence between nt -209 and -191 which partially overlaps the glucocorticoid receptor binding sites I and II. This site has homology with the known binding site for hepatocyte nuclear factor 1 (HNF1). ADH2 promoter DNA fragments containing various lengths of 5'-flanking sequences were fused upstream from the gene encoding chloramphenicol acetyltransferase (cat) and transfected into the HepG2 human hepatoma cell line. The resulting cat expression was subject to induction by dexamethasone in constructions containing ADH2 DNA between nt -272 and -171. This indicates that the glucocorticoid receptor binding sites identified by footprint analysis function as a glucocorticoid response element (GRE) in a liver cell line. Heterologous ADH-cat fusions, in which the ADH2-GRE was fused to the adenovirus major late promoter, exhibited glucocorticoid induction of cat expression in CV-1B cells when cotransfected with a glucocorticoid receptor expression vector. Glucocorticoid regulation in CV-1B was observed when either all three glucocorticoid receptor binding sites (sites 0, I, II) or the two distal sites (sites 0, I) were present. Overall, these results indicate that the ADH2 gene possesses a functional GRE which can potentially regulate expression transcriptionally.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A hormone response element upstream from the human alcohol dehydrogenase gene ADH2 consists of three tandem glucocorticoid receptor binding sites. 221 Mar 83

The effect of glucocorticoids on gene expression of rat class I alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) was investigated. A cDNA clone for the beta-subunit of human ADH (ADH2) was used to analyze class I ADH mRNA levels in rat hepatoma cells, which are known to contain a functional glucocorticoid receptor. RNA gel blot analysis of total cellular RNA isolated from these cells showed hybridization of the human ADH2 cDNA probe to a single approximately equal to 1500-base RNA species. Treatment of the cells with dexamethasone (0.1 nM to 1 microM) caused a dose-dependent increase in total cellular class I ADH mRNA levels by a factor of 2-4. Maximal levels were reached within 18-24 hr of treatment. This effect was reversible following withdrawal of dexamethasone. The glucocorticoid induction of class I ADH mRNA does not seem to require ongoing protein synthesis since treatment of the cells with cycloheximide did not affect the increase in class I ADH mRNA levels by dexamethasone. The human ADH2 gene contains both upstream and within the coding region sequence motifs that display homology with response elements of genes positively regulated by glucocorticoids. These data suggest a receptor-mediated transcriptional enhancement of the ADH2 gene as the mechanism of regulation. However, analysis of RNA decay in cells treated with actinomycin D indicates that the dexamethasone-induced increase in class I ADH mRNA might, at least in part, be due to enhanced ADH mRNA stability.
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PMID:Regulation of gene expression of class I alcohol dehydrogenase by glucocorticoids. 342 58

MAP kinases JNK and p38 play an important role in many immune and inflammatory processes, whereas glucocorticoids exert immunosuppressive and anti-inflammatory activities. We found previously that activation of p38 or JNK inhibits glucocorticoid receptor (GR)-mediated transcriptional activation of a mouse mammary tumor virus (MMTV) promoter-driven luciferase construct in HeLa cells. It appears that this effect is DNA regulatory element-specific, since p38 or JNK activation stimulates GR-dependent transcription from TAT3-ADH promoter-luciferase construct in the same cells. The apparent promoter-specificity of this action suggests that not all glucocorticoid-activated genes are negatively regulated by p38 or JNK. Using different MMTV/TAT3 chimeric reporters we demonstrate that the presence of other accessory binding sites of the MMTV construct contributes to the inhibitory effect of activated p38 or JNK on the MMTV-driven transcriptional activity; and diminishes, but does not reverse the stimulation observed using the TAT GREs from the TAT3-ADH promoter-luciferase construct. On the other hand, comparison of the effects of GRE sequences, either in isolation or in the context of the MMTV LTR accessory binding sites, demonstrates that the responsiveness of the GR depends on the GRE sequence; indicating that in addition to transcription factors bound nearby, interaction with the DNA itself modulates GR activity.
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PMID:Promoter-context as a determinant of glucocorticoid receptor-responsiveness to activation of p38 and JNK mitogen-activated protein (MAP) kinases. 2304 44