Wright Eric J, De Castro Karen Pereira, Joshi Aditya D, Elferink Cornelis J
Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0654, USA.
Curr Opin Toxicol. 2017 Feb;2:87-92. doi: 10.1016/j.cotox.2017.01.001. Epub 2017 Jan 18.
Decades of research on the Aryl hydrocarbon Receptor (AhR) has unveiled its involvement in the toxicity of halogenated and polycyclic aromatic hydrocarbons, and a myriad of normal physiological processes. The molecular dissection of AhR biology has centered on a canonical signaling pathway in an effort to mechanistically reconcile the diverse pathophysiological effects of exposure to environmental pollutants. As a consequence, we now know that canonical signaling can explain many but not all of the AhR-mediated effects. Here we describe recent findings that point to non-canonical signaling pathways, and focus on a novel AhR interaction with the Krüppel-like Factor 6 protein responsible for previously un-recognized epigenetic changes in the chromatin affecting gene expression.
数十年来对芳烃受体（AhR）的研究揭示了其在卤代烃和多环芳烃毒性以及众多正常生理过程中的作用。AhR生物学的分子剖析主要围绕一条经典信号通路展开，旨在从机制上解释接触环境污染物所产生的各种病理生理效应。因此，我们现在知道经典信号通路可以解释许多但并非所有由AhR介导的效应。在此，我们描述了指向非经典信号通路的近期研究发现，并着重关注AhR与Krüppel样因子6蛋白的一种新型相互作用，该相互作用导致染色质中发生此前未被认识到的表观遗传变化，进而影响基因表达。
