| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Research Abstract |
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
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