Mechanism and biological consequences of the nuclear rec

控制药物代谢酶的一个基本原则是它们广泛的结构多样性与特异性的松散联系。许多调节蛋白决定酶的诱导。这些蛋白质中的一些还表现出结构多样性和功能混杂性，这也可能是蛋白质修饰和蛋白质-蛋白质相互作用的反映。我们的基础研究旨在了解控制代谢酶功能的潜在结构基础以及调节酶表达的蛋白质。我们选择研究苯巴比妥（PB）诱导的分子和细胞机制。PB是一组能够诱导药物代谢酶的外源性物质，其诱导作用的一个显著特征是它的多效性改变了大量肝脏基因的表达，其中一些改变是相互协调的，以达到生理和/或药理学终点。PB还作为肿瘤促进剂，在啮齿动物中引起肝细胞癌。PB的这些多效性作用由核受体CAR的活化介导。

An underlying principle that governs drug-metabolizing enzymes is their broad structural diversity with a loose link to specificity. Numerous regulatory proteins dictate induction of the enzymes. Some of these proteins also exhibit structural diversity and functional promiscuity, which may also be a reflection of protein modifications and protein-protein interactions. Our basic research aims are to understand the underlying structural basis governing the functions of metabolic enzymes and the proteins that regulate expression of the enzymes. We have chosen to investigate molecular and cellular mechanisms of phenobarbital (PB) induction. PB represents a group of myriad xenobiotics that induce drug-metabolizing enzymes.A signature of PB induction is its pleiotropicity altering the expression of a large number of hepatic genes.Some of those alterations are coordinated to achieve a physiological and/or pharmacological end-point. PB also acts as tumor promoter, causing hepatocellular carcinomas in rodents. These pleiotropic actions of PB are mediated by the activation of nuclear receptor CAR.