The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene
| Autor: | Takeshi Kawamoto, Paavo Honkakoski, Igor Zelko, Masahiko Negishi, Tatsuya Sueyoshi |
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| Rok vydání: | 1999 |
| Předmět: |
Molecular Sequence Data
Receptors Cytoplasmic and Nuclear Biology Retinoid X receptor Transfection Biochemistry Gene Expression Regulation Enzymologic Cytochrome P-450 Enzyme System Constitutive androstane receptor Tumor Cells Cultured Humans Enhancer Molecular Biology Transcription factor Nuclear receptor co-repressor 1 Constitutive Androstane Receptor Regulation of gene expression Expression vector Base Sequence Oxidoreductases N-Demethylating Cell Biology Molecular biology Cytochrome P-450 CYP2B6 Nuclear receptor Phenobarbital Trans-Activators Aryl Hydrocarbon Hydroxylases Excitatory Amino Acid Antagonists Signal Transduction Transcription Factors |
| Zdroj: | The Journal of biological chemistry. 274(10) |
| ISSN: | 0021-9258 |
| Popis: | The endogenous CYP2B6 gene becomes phenobarbital (PB) inducible in androstenol-treated HepG2 cells either transiently or stably transfected with a nuclear receptor CAR expression vector. The PB induction mediated by CAR is regulated by a conserved 51-base pair element called PB-responsive enhancer module (PBREM) that has now been located between -1733 and -1683 bp in the gene's 5'-flanking region. An in vitro translated CAR acting as a retinoid X receptor alpha heterodimer binds directly to the two nuclear receptor sites NR1 and NR2 within PBREM. In a stably transfected HepG2 cell line, both PBREM and NR1 are activated by PB and PB-type compounds such as chlorinated pesticides, polychlorinated biphenyls and chlorpromazine. In addition to PBREM, CAR also transactivates the steroid/rifampicin-response element of the human CYP3A4 gene in HepG2 cells. Thus, activation of the repressed nuclear receptor CAR appears to be a versatile mediator that regulates PB induction of the CYP2B and other genes. |
| Databáze: | OpenAIRE |
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