Interaction of PER2 with the constitutive androstane receptor possibly links circadian rhythms to metabolism

Abstract

Period 2 (PER2) is an important factor in daily oscillations called circadian rhythms, which are emerging as one of the most important regulatory networks, responsible for homeostasis and transcriptional regulation of a number of genes. Our work shows that PER2 could act as a co-activator of the constitutive androstane receptor (CAR), a key nuclear receptor (NR) that regulates the metabolism of endobiotics and xenobiotics. Bioinformatic analysis shows that PER2 and CAR possess structural elements that could enable them to interact which was confirmed experimentally by CoIP experiment. Co-transfection of mouse hepatocarcinoma cells with plasmids overexpressing Per2 and Car increases expression of Bmal1, a potential CAR target gene, more than transfections with Car only. This is the first report indicating the interaction of PER2 and CAR.