Tripartite Motif Containing 24 Acts as a Novel Coactivator of the Constitutive Active/Androstane Receptor.

The tripartite motif containing 24 acts as a novel coactivator of the constitutive active/androstane receptor

Activation of Orphan Nuclear Constitutive Androstane Receptor Requires Subnuclear Targeting by Peroxisome Proliferator-activated Receptor Coactivator-1 A POSSIBLE LINK BETWEEN XENOBIOTIC RESPONSE AND NUTRITIONAL STATE*

In contrast to the classical nuclear receptors, the constitutive androstane receptor (CAR) is transcriptionally active in the absence of ligand. In the course of searching for the mediator of CAR activation, we found that ligand-independent activation of CAR was achieved in cooperation with the peroxisome proliferator-activated receptor coactivator-1 (PGC-1 ). PGC-1 , a PGC-1 homologue, also ac...

Residue threonine 350 confers steroid hormone responsiveness to the mouse nuclear orphan receptor CAR.

Steroid hormones modulate activity of the nuclear receptor constitutive active receptor (CAR, or constitutive androstane receptor) in mouse liver. Progesterone and testosterone repress the constitutive activity of mouse CAR (mCAR) in cell-mediated transfection assays, whereas estrogens activate the repressed receptor. This repression and activation is not observed with human CAR. To define the ...

Nigramide J is a novel potent inverse agonist of the human constitutive androstane receptor

The constitutive androstane receptor (CAR, NR1I3) is very important for drug development and for understanding pharmacokinetic drug-drug interactions. We screened by mammalian one hybrid assay among natural compounds to discover novel ligands of human constitutive androstane receptor (hCAR). hCAR transcriptional activity was measured by luciferase assay and mRNA levels of CYP2B6 and CYP3A4 in H...

The peripheral benzodiazepine receptor ligand 1-(2-chlorophenyl-methylpropyl)-3-isoquinoline-carboxamide is a novel antagonist of human constitutive androstane receptor.

As a promiscuous xenobiotic sensor, the constitutive androstane receptor (CAR; NR1I3) regulates the expression of multiple drug-metabolizing enzymes and transporters in liver. The constitutively activated nature of CAR in the cell-based transfection assays has hindered its use as a predictor of metabolism-based drug-drug interactions. Here, we have identified 1-(2-chlorophenylmethylpropyl)-3-is...