Role reversal: new insights from new ligands for the xenobiotic receptor CAR

In the classic model of nuclear receptor signaling, specific hormone bindin g results in the recruitment of coactivator proteins and transcriptional ac tivation. Recent results with newly characterized nuclear receptors have ex panded this model to include new types of ligands and novel transcriptional responses. Both inverse agonists and conventional agonist ligands have bee n identified for the xenobiotic receptor constitutive androstane receptor ( CAR), a constitutive activator of transcription in the absence of ligands.