Constitutive Androstane Receptor-1 (CAR-1; NR1I3i1)

Also available in: Rat, Mouse

Human Constitutive Androstane Receptor-1 (CAR-1) exhibits constitutive activity, but can be further regulated through direct ligand interactions. The primary application of this reporter assay system is in the screening of test samples to quantify any functional inverse-agonist activity that they may exert on human CAR-1. INDIGO’s CAR-1 Reporter Assay System utilizes proprietary mammalian cells engineered to provide high-level expression of human CAR-1 (NR1I3 isoform 1), which is a constitutively active transcription factor.

Reporter Cells utilize a modified version of human CAR1 in which the N-terminal DNA binding domain (DBD) has been replaced with the GAL4-DBD. The human CAR1 ligand binding domain (LBD) is unaltered and fully functional. These reporter cells also incorporate a luciferase cDNA functionally linked to the GAL4-upstream activation sequence (UAS). Thus, quantifying expressed luciferase activity provides a sensitive surrogate measure of changes in CAR1 activity resulting from a direct interaction between a treatment compound and the nuclear receptor. Because this assay system expresses a GAL4-DBD + hCAR1 LBD hybrid receptor, the bio-activity of activators that act through indirect mechanisms (such as those that alter the phosphorylation status of the native N-terminal amino acid sequence of CAR1) may be dampened or go undetected.

CAR is encoded by the NR1I3 gene. This gene encodes a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. The protein binds to DNA as a monomer or a heterodimer with the retinoid X receptor and regulates the transcription of target genes involved in drug metabolism and bilirubin clearance, such as cytochrome P450 family members. Unlike most nuclear receptors, this transcriptional regulator is constitutively active in the absence of ligand but is regulated by both agonists and inverse agonists. Ligand binding results in translocation of this protein to the nucleus, where it activates or represses target gene transcription. These ligands include bilirubin, a variety of foreign compounds, steroid hormones, and prescription drugs.

The principle application of this assay product is in the screening of test samples to quantify functional inverse-agonist activities that they may exert against the human constitutive androstane receptor.

For more information on CAR, visit the Nuclear Receptor Resource.

Synonyms:Constitutive Androstane Receptor-1, CAR-1, NR1I3i1