Linked Life Data

8106494

Source:http://linkedlifedata.com/resource/pubmed/id/8106494

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1994-3-22
pubmed:abstractText
The intracellular basic helix-loop-helix (bHLH) dioxin receptor mediates signal transduction by dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin). In analogy to nuclear receptors that are members of the steroid hormone receptor superfamily the dioxin receptor is a ligand-inducible transcriptional regulator that directly binds to response elements within regulated genes. The most commonly studied dioxin receptor ligands are dioxin itself and structurally related environmental contaminants. A physiological ligand has not yet been identified. Interestingly, however, indolo[3,2-b]carbazole, a compound formed from precursors in the diet, has been shown to bind the murine dioxin receptor with high affinity in vitro. In the present study we show that this compound and its methylated derivative 5,11-dimethylindolo[3,2-b]carbazole very potently activated transcription from a dioxin or xenobiotic response element (XRE)-driven reporter gene in both murine and human hepatoma cells. This effect was not observed in mutant, dioxin-resistant hepatoma cells which are either deficient in expression of dioxin receptor or the bHLH receptor partner factor Arnt. In vitro indolocarbazoles induced XRE binding activity by the human dioxin receptor-Arnt complex in a dose-dependent manner. Thus, both dioxin- and indolocarbazole-activated forms of dioxin receptor regulate target gene expression by the same mechanism involving recruitment of the bHLH factor Arnt and recognition of the XRE element. Finally, the indolo[3,2-b]carbazole-activated human dioxin receptor appeared to generate more stable complexes with the XRE target sequence relative to those produced by the dioxin-activated receptor form, indicating interesting mechanistic differences between different classes of dioxin receptor ligands in their abilities to modulate human dioxin receptor function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5137-44
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8106494-Animals, pubmed-meshheading:8106494-Carbazoles, pubmed-meshheading:8106494-Carcinoma, Hepatocellular, pubmed-meshheading:8106494-Cell Line, pubmed-meshheading:8106494-DNA-Binding Proteins, pubmed-meshheading:8106494-Diet, pubmed-meshheading:8106494-Dimethyl Sulfoxide, pubmed-meshheading:8106494-Gene Expression, pubmed-meshheading:8106494-Helix-Loop-Helix Motifs, pubmed-meshheading:8106494-Humans, pubmed-meshheading:8106494-Indoles, pubmed-meshheading:8106494-Kinetics, pubmed-meshheading:8106494-Liver Neoplasms, pubmed-meshheading:8106494-Mice, pubmed-meshheading:8106494-Receptors, Aryl Hydrocarbon, pubmed-meshheading:8106494-Signal Transduction, pubmed-meshheading:8106494-Structure-Activity Relationship, pubmed-meshheading:8106494-Tetrachlorodibenzodioxin, pubmed-meshheading:8106494-Transfection, pubmed-meshheading:8106494-Tumor Cells, Cultured
pubmed:year
1994
pubmed:articleTitle
Regulation of human dioxin receptor function by indolocarbazoles, receptor ligands of dietary origin.
pubmed:affiliation
Department of Medical Nutrition, Karolinska Institutet, Huddinge University Hospital, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't