The DHR96 nuclear receptor regulates xenobiotic responses in Drosophila
The DHR96 nuclear receptor regulates xenobiotic responses in Drosophila
复制标题
DOI：
10.1016/j.cmet.2006.06.006
复制
发表时间：
2006-07-01
期刊：
影响因子：
29
通讯作者：
Thummel, Carl S.
中科院分区：
文献类型：
--
作者：
King-Jones, Kirst;Horner, Michael A.;Thummel, Carl S.
暴露于植物毒素、污染物或处方药等外源性物质会引发防御反应，诱导编码关键解毒酶的基因。虽然异生素反应已在脊椎动物中进行了研究，很少有人努力利用一个简单的遗传系统来表征这种协调的转录反应的分子基础。我们在这里表明，类似1000成绩单显着影响苯巴比妥治疗果蝇。我们还证明了果蝇的人类SXR和CAR异生素受体的直系同源物，DHR 96，在这种反应中发挥作用。DHR96无效突变体显示对苯巴比妥和杀虫剂DDT的镇静作用的敏感性增加，以及许多苯巴比妥调节基因表达的缺陷。代谢和应激反应基因也由DHR96控制，暗示其在协调多种反应途径中的作用。这项工作建立了一个新的模型系统，以确定外源胁迫反应的遗传控制。
Exposure to xenobiotics such as plant toxins, pollutants, or prescription drugs triggers a defense response, inducing genes that encode key detoxification enzymes. Although xenobiotic responses have been studied in vertebrates, little effort has been made to exploit a simple genetic system for characterizing the molecular basis of this coordinated transcriptional response. We show here that similar to 1000 transcripts are significantly affected by phenobarbital treatment in Drosophila. We also demonstrate that the Drosophila ortholog of the human SXR and CAR xenobiotic receptors, DHR96, plays a role in this response. A DHR96 null mutant displays increased sensitivity to the sedative effects of phenobarbital and the pesticide DDT as well as defects in the expression of many phenobarbital-regulated genes. Metabolic and stress-response genes are also controlled by DHR96, implicating its role in coordinating multiple response pathways. This work establishes a new model system for defining the genetic control of xenobiotic stress responses.