[Regulation of cytochrome P-450 (CYP) genes by nuclear receptors].
Many xenobiotics are metabolized and detoxified by cytochrome P-450s (CYP). The xenobiotics metabolizing CYPs are induced by various kinds of receptors. To induce CYP1A1, the Ah receptor requires a ligand for its activation as a transcription factor. On the other hand, benzimidazole compounds can induce CYP1A1 without binding to the Ah receptor as a ligand (ligand-independent pathway). In response to phenobarbital (PB) and other PB-type inducers, the nuclear receptor CAR (the NR-constitutive active receptor) translocates to the nucleus, forms a dimer with the retinoid X receptor (RXR), and activates the PB-responsive enhancer module (PBREM) in the PB-inducible CYP2B genes. For human CYP3A4 genes, pregnane X receptor (PXR) binds to the xenobiotic-responsive enhancer module (XREM) and upon induction by rifampicin, a PXR:RXR heterodimer could transactivate XREM.
Kikuchi
Hideaki
H
Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. hkikuchi@idac.tohoku.ac.jp
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D006801:Humans; D015262:Xenobiotics / Q000378:metabolism
D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1