The Nuclear Orphan Receptor CAR-Retinoid X Receptor Heterodimer Activates the Phenobarbital-Responsive Enhancer Module of the CYP2B Gene
| Autor: | Masahiko Negishi, Tatsuya Sueyoshi, Paavo Honkakoski, Igor Zelko |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Time Factors Receptors Retinoic Acid Molecular Sequence Data Receptors Cytoplasmic and Nuclear Gene Expression Biology Retinoid X receptor Mice Cytochrome P-450 Enzyme System Constitutive androstane receptor Tumor Cells Cultured Animals Humans Amino Acid Sequence Cytochrome P450 Family 2 Molecular Biology Transcription factor Cells Cultured Constitutive Androstane Receptor Nuclear receptor co-repressor 1 Orphan receptor Pregnane X receptor Binding Sites Cell Biology Molecular biology Neuron-derived orphan receptor 1 body regions Mice Inbred C57BL Enhancer Elements Genetic Retinoid X Receptors nervous system Gene Expression Regulation Nuclear receptor Phenobarbital Steroid Hydroxylases embryonic structures Trans-Activators lipids (amino acids peptides and proteins) Aryl Hydrocarbon Hydroxylases Dimerization hormones hormone substitutes and hormone antagonists Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 18:5652-5658 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.18.10.5652 |
| Popis: | PBREM, the phenobarbital-responsive enhancer module of the cytochrome P-450 Cyp2b10 gene, contains two potential nuclear receptor binding sites, NR1 and NR2. Consistent with the finding that anti-retinoid X receptor (RXR) could supershift the NR1-nuclear protein complex, DNA affinity chromatography with NR1 oligonucleotides enriched the nuclear orphan receptor RXR from the hepatic nuclear extracts of phenobarbital-treated mice. In addition to RXR, the nuclear orphan receptor CAR was present in the same enriched fraction. In the phenobarbital-treated mice, the binding of both CAR and RXR was rapidly increased before the induction of CYP2B10 mRNA. In vitro-translated CAR bound to NR1, but only in the presence of similarly prepared RXR. PBREM was synergistically activated by transfection of CAR and RXR in HepG2 and HEK293 cells when the NR1 site was functional. A CAR-RXR heterodimer has thus been characterized as a trans-acting factor for the phenobarbital-inducible Cyp2b10 gene. |
| Databáze: | OpenAIRE |
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