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Phenobarbital Response Elements of Cytochrome P450 Genes and Nuclear Receptors
Abstract
Phenobarbital (PB) response elements are composed of various nuclear receptor (NR)-binding sites. A 51-bp distal element PB-responsive enhancer module (PBREM) conserved in the PB-inducible CYP2B genes contains two NR-binding direct repeat (DR)-4 motifs. Responding to PB exposure in liver, the NR constitutive active receptor (CAR) translocates to the nucleus, forms a dimer with the retinoid X receptor (RXR), and activates PBREM via binding to DR-4 motifs. For CYP3A genes, a common NR site [DR-3 or everted repeat (ER)-6] is present in proximal promoter regions. In addition, the distal element called the xenobiotic responsive module (XREM) is found in human CYP3A4 genes, which contain both DR-3 and ER-6 motifs. Pregnane X receptor (PXR) could bind to all of these sites and, upon PB induction, a PXR:RXR heterodimer could transactivate XREM. These response elements and NRs are functionally versatile, and capable of responding to distinct but overlapping groups of xenochemicals.
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The Aryl Hydrocarbon Receptor Complex
Hankinson, O. (1995) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.35.040195.001515 · Cited by 1,649
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Ueda, A., Hamadeh, H. K., Webb, H. K., Yamamoto, Y., Sueyoshi, T., Afshari, C. A., Lehmann, J. M., & Negishi, M. (2002) · Molecular Pharmacology · doi:10.1124/mol.61.1.1 · Cited by 466
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Metadata
- Authors
- Sueyoshi, T., & Negishi, M.
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2001-04
- Volume
- 41
- Issue
- 1
- Pages
- 123-143
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- OpenAlex
- W2136070698
- Cited by
- 362
- References
- 1
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- closed
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