The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Reciprocal activation of Xenobiotic response genes by nuclear receptors SXR/PXR and CAR
Open accessAbstract
The cytochrome P450 (CYP) gene products such as CYP3A and CYP2B are essential for the metabolism of steroid hormones and xenochemicals including prescription drugs. Nuclear receptor SXR/PXR (steroid and xenobiotic receptor/pregnenolone X receptor) has been shown both biochemically and genetically to activate CYP3A genes, while similar studies have established constitutive androstane receptor (CAR) as a CYP2B regulator. The response elements in these genes are also distinct, furthering the concept of independent regulation. Unexpectedly, we found that SXR can regulate CYP2B, both in cultured cells and in transgenic mice via adaptive recognition of the phenobarbital response element (PBRE). In a type of functional symmetry, orphan receptor CAR was also found to activate CYP3A through previously defined SXR/PXR response elements. These observations not only provide a rational explanation for the activation of multiple CYP gene classes by certain xenobiotics, but also reveal the existence of a metabolic safety net that confers a second layer of protection to the harmful effects of toxic compounds and at the same time increases the propensity for drug–drug interactions.
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Citations
Cites
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 · cited 1×
“The AH receptor itself binds dioxin and other structurally similar polycyclic aromatic hydrocarbons to activate the cognate xenobiotic response element of the CYP1A and CYP1B1 genes (Hankinson 1995; Whitlock et al. 1996).”
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Cited by
Bile salt transporters: molecular characterization, function, and regulation
Trauner, M., & Boyer, J. L. (2003) · Physiological Reviews · doi:10.1152/physrev.00027.2002 · Cited by 999
Kast, H. R., Goodwin, B., Tarr, P. T., Jones, S. A., Anisfeld, A. M., Stoltz, C. M., Tontonoz, P., Kliewer, S., Willson, T. M., & Edwards, P. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109326200 · Cited by 916
Hewitt, N. J., Gómez Lechón, M. J., Houston, J. B., Hallifax, D., Brown, H. S., Maurel, P., Kenna, J. G., Gustavsson, L., Lohmann, C., Skonberg, C., et al. (2007) · Drug Metabolism Reviews · doi:10.1080/03602530601093489 · Cited by 735
LeCluyse, E. L. (2001) · European Journal of Pharmaceutical Sciences · doi:10.1016/s0928-0987(01)00135-x · Cited by 477
Guo, G. L., Lambert, G., Negishi, M., Ward, J. M., Brewer, H. B., Kliewer, S. A., Gonzalez, F. J., & Sinal, C. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307145200 · Cited by 312
Metadata
- Authors
- Xie, W., Barwick, J. L., Simon, C. M., Pierce, A. M., Safe, S., Blumberg, B., Guzelian, P. S., & Evans, R. M.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2000-12-01
- Volume
- 14
- Issue
- 23
- Pages
- 3014-3023
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2155882942
- Cited by
- 508
- References
- 1
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Xie, W., Barwick, J. L., Simon, C. M., Pierce, A. M., Safe, S., Blumberg, B., Guzelian, P. S., & Evans, R. M. (2000). Reciprocal activation of Xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes & Development. https://doi.org/10.1101/gad.846800
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