Activation Mechanism of the nuclear receptor CAR

支配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。许多调节蛋白决定了酶的诱导。其中一些蛋白质还表现出结构多样性和功能混杂，这也可能是蛋白质修饰和蛋白质相互作用的反映。我们的基本研究目标是了解控制代谢酶功能的潜在结构基础和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代表了一组无数的诱导药物代谢酶的异种生物。铅诱导的一个特征是其多效性改变了大量肝脏基因的表达。其中一些改变是协调的，以达到生理和/或药理学的终点。PB还可作为肿瘤促进剂，在啮齿类动物中引起肝细胞癌。

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.