Furness Sebastian G B, Lees Michael J, Whitelaw Murray L
Drug Discovery Laboratory, Department of Pharmacology, Building 13E, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
FEBS Lett. 2007 Jul 31;581(19):3616-25. doi: 10.1016/j.febslet.2007.04.011. Epub 2007 Apr 17.
This review examines the common theme of adaptive responses of bHLH/PAS proteins, using the dioxin receptor as a prototype. The bHLH/PAS family of transcriptional regulators are a group of key developmental and environmental stress sensing proteins. They employ a variety of post-translational control mechanisms to regulate their transcriptional output. Amongst this family, the dioxin receptor is best known for its ability to elicit toxic responses to dioxin and dioxin like chemicals even though it mediates more benign adaptive responses to non-toxic xenobiotics. We discuss what is known about dioxin receptor physiology, both adaptive and inherent, along with its molecular regulation and put this into the context of the wider bHLH/PAS family. We also raise the issue of its toxic responses, in particular the idea that it is the dysregulation of its poorly characterised housekeeping functions that leads to these outcomes.
本综述以二噁英受体为原型，探讨了bHLH/PAS蛋白适应性反应的共同主题。转录调节因子的bHLH/PAS家族是一组关键的发育和环境应激传感蛋白。它们采用多种翻译后控制机制来调节其转录输出。在这个家族中，二噁英受体最为人所知的是它能够引发对二噁英和二噁英类化学物质的毒性反应，尽管它介导了对无毒外源性物质的更良性的适应性反应。我们讨论了关于二噁英受体生理学的已知信息，包括适应性和固有性，以及其分子调节，并将其置于更广泛的bHLH/PAS家族的背景下。我们还提出了其毒性反应的问题，特别是认为其特征不明确的管家功能失调导致了这些结果的观点。
