ArticleThe Journal of biological chemistry2008
Nuclear receptor CAR requires early growth response 1 to activate the human cytochrome P450 2B6 gene.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Nuclear receptor phosphorylation in xenobiotic signal transduction.The Journal of biological chemistry · 2020Review
- Ser100-Phosphorylated RORMolecular pharmacology · 2020Article
- Transcriptomic profiling identifies novel mechanisms of transcriptional regulation of the cytochrome P450 (Cyp)3a11 gene.Scientific reports · 2019Article
- Article
- Pregnane X receptor promotes ethanol-induced hepatosteatosis in mice.The Journal of biological chemistry · 2018Article
- Insights into CYP2B6-mediated drug-drug interactions.Acta pharmaceutica Sinica. B · 2016Review
- p38 MAP Kinase Links CAR Activation and Inactivation in the Nucleus via Phosphorylation at Threonine 38.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Coordinated regulation of nuclear receptor CAR by CCRP/DNAJC7, HSP70 and the ubiquitin-proteasome system.PloS one · 2014Article
- p38 Mitogen-activated protein kinase regulates nuclear receptor CAR that activates the CYP2B6 gene.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Liganded pregnane X receptor represses the human sulfotransferase SULT1E1 promoter through disrupting its chromatin structure.Nucleic acids research · 2011Article
- Nuclear receptor CAR-regulated expression of the FAM84A gene during the development of mouse liver tumors.International journal of oncology · 2011Article
- NCOA6 differentially regulates the expression of the CYP2C9 and CYP3A4 genes.Pharmacological research · 2011Article
- Nonviral gene transfer as a tool for studying transcription regulation of xenobiotic metabolizing enzymes.Advanced drug delivery reviews · 2010Review
- CCAAT/enhancer-binding protein alpha (C/EBPalpha) and hepatocyte nuclear factor 4alpha (HNF4alpha) synergistically cooperate with constitutive androstane receptor to transactivate the human cytochrome P450 2B6 (CYP2B6) gene: application to the development of a metabolically competent human hepatic cell model.The Journal of biological chemistry · 2010Article
- Early growth response 1 loops the CYP2B6 promoter for synergistic activation by the distal and proximal nuclear receptors CAR and HNF4alpha.FEBS letters · 2009Article
- Antiepileptic drugs reduce efficacy of methotrexate chemotherapy by downregulation of Reduced folate carrier transport activity.Leukemia · 2009Article
- CYP2B6: new insights into a historically overlooked cytochrome P450 isozyme.Current drug metabolism · 2008Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The nuclear receptor CAR (constitutive active/androstane receptor) is a drug-sensing transcription factor, regulating the hepatic genes that encode various drug-metabolizing enzymes. We have now characterized the novel regulatory mechanism by which the signal molecule EGR1 (early growth response 1) determines CAR-mediated activation of the human CYP2B6 (cytochrome P450 2B6) gene. The CYP2B6 enzyme metabolizes commonly used therapeutics and also activates pro-drugs. The CAR directly binds to the distal enhancer element of the CYP2B6 promoter, which is essential in converging to its drug-sensing function onto promoter activity. However, this binding alone is not sufficient to activate the CYP2B6 promoter; the promoter requires EGR1 to enable CAR to activate the CYP2B6 promoter. Upon stimulation by protein kinase C, EGR1 directly binds to the proximal promoter and coordinates the nearby HNF4alpha (hepatocyte-enriched nuclear factor 4alpha) with CAR at the distal enhancer element to activate the promoter. Thus, synergy of drug activation and the stimulation of cellular signal are necessary for CAR to activate the CYP2B6 gene.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.