Activation Mechanism of the nuclear receptor CAR

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，与特异性有松散的联系。许多调节蛋白决定了这些酶的诱导。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。我们的基本研究目的是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是一组诱导药物代谢酶的外源化合物。PB诱导的一个特征是它的多效性改变了大量肝脏基因的表达。这些改变中的一些被协调以达到生理和/或药物的终点。PB还作为肿瘤促进剂，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.