Studies on the activation mechanism of xenobiotic-responsive nuclear receptor CAR and establishment of in vitro evaluation system for its ligands

包括人类在内的动物对药物化合物和环境污染物等外源物的毒性具有防御机制。组成型雄甾受体（CAR）通过转录激活代谢酶、转运蛋白等靶基因，在这一防御机制中发挥重要作用。本研究阐明了微管网络和输入蛋白/Ran系统在原代肝细胞中激活剂介导的CAR核易位中发挥了重要作用。然而，在不朽的细胞中，无配体的CAR会自发地转移到核室中，在那里它会激活靶基因。利用配体依赖性的CAR突变体，在不牺牲动物的情况下，建立了新的CAR配体筛选系统。所有这些发现不仅有助于了解d

Animals including human beings have a defense mechanism against the toxicity of xenobiotics such as medicinal compounds and environmental pollutants. The constitutive androstane receptor (CAR) plays an important role in this defense mechanism by transcriptionally activating target genes coding for the metabolic enzymes, transporters and so on. In this study, it was elucidated that the microtubule network and importin/Ran system played important roles in the activator mediated nuclear translocation of CAR in primary hepatocytes. In immortal cells, however, the ligand-free CAR is spontaneously translocated into the nuclear compartment where it transactivates target genes. Using the ligand-dependent CAR mutant, the novel screening system for CAR ligand was established without sacrificing animals. All these findings will be beneficial in not only understanding of the d