ArticleMolecular endocrinology (Baltimore, Md.)2012
Evolutionary history and functional characterization of the amphibian xenosensor CAR.
Article in Molecular endocrinology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 32 citations in OpenAlex.
- The assessment for potential thyroid-mediated endocrine disruption in amphibians: Clarification on the use of new methods and on the interpretation of changes in thyroid histology.EFSA journal. European Food Safety Authority · 2025Article
- The hypolipidemic effect of MI-883, the combined CAR agonist/ PXR antagonist, in diet-induced hypercholesterolemia model.Nature communications · 2025Article
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- Role of nuclear pregnane X receptor in Cu-induced lipid metabolism and xenobiotic responses in largemouth bass (Frontiers in endocrinology · 2022Article
- Evolutionary Plasticity in Detoxification Gene Modules: The Preservation and Loss of the Pregnane X Receptor in Chondrichthyes Lineages.International journal of molecular sciences · 2019Article
- Independent losses of a xenobiotic receptor across teleost evolution.Scientific reports · 2018Article
- Annotation of the Nuclear Receptors in an Estuarine Fish species,Nuclear receptor research · 2017Article
- Small-molecule modulators of PXR and CAR.Biochimica et biophysica acta · 2016Review
- Acetylation of lysine 109 modulates pregnane X receptor DNA binding and transcriptional activity.Biochimica et biophysica acta · 2016Article
- Role of pregnane X receptor and aryl hydrocarbon receptor in transcriptional regulation of pxr, CYP2, and CYP3 genes in developing zebrafish.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- The lineage-specific evolution of aquaporin gene clusters facilitated tetrapod terrestrial adaptation.PloS one · 2014Article
- Structural and functional similarity of amphibian constitutive androstane receptor with mammalian pregnane X receptor.PloS one · 2014Article
- Functional characterization of a full length pregnane X receptor, expression in vivo, and identification of PXR alleles, in zebrafish (Danio rerio).Aquatic toxicology (Amsterdam, Netherlands) · 2013Article
- The cytochrome P450 2AA gene cluster in zebrafish (Danio rerio): expression of CYP2AA1 and CYP2AA2 and response to phenobarbital-type inducers.Toxicology and applied pharmacology · 2013Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The xenosensing constitutive androstane receptor (CAR) is widely considered to have arisen in early mammals via duplication of the pregnane X receptor (PXR). We report that CAR emerged together with PXR and the vitamin D receptor from an ancestral NR1I gene already in early vertebrates, as a result of whole-genome duplications. CAR genes were subsequently lost from the fish lineage, but they are conserved in all taxa of land vertebrates. This contrasts with PXR, which is found in most fish species, whereas it is lost from Sauropsida (reptiles and birds) and plays a role unrelated to xenosensing in Xenopus. This role is fulfilled in Xenopus by CAR, which exhibits low basal activity and pronounced responsiveness to activators such as drugs and steroids, altogether resembling mammalian PXR. The constitutive activity typical for mammalian CAR emerged first in Sauropsida, and it is thus common to all fully terrestrial land vertebrates (Amniota). The constitutive activity can be achieved by humanizing just two amino acids of the Xenopus CAR. Taken together, our results provide a comprehensive reconstruction of the evolutionary history of the NR1I subfamily of nuclear receptors. They identify CAR as the more conserved and remarkably plastic NR1I xenosensor in land vertebrates. Nonmammalian CAR should help to dissect the specific functions of PXR and CAR in the metabolism of xeno- and endobiotics in humans. Xenopus CAR is a first reported amphibian xenosensor, which opens the way to toxicogenomic and bioaugmentation studies in this critically endangered taxon of land vertebrates.
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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.