Avilla Mele N, Malecki Kristen M C, Hahn Mark E, Wilson Rachel H, Bradfield Christopher A
Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts 02543-1050, United States.
McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705-227, United States.
Chem Res Toxicol. 2020 Apr 20;33(4):860-879. doi: 10.1021/acs.chemrestox.9b00476. Epub 2020 Apr 7.
The Ah receptor (AHR) has been studied for almost five decades. Yet, we still have many important questions about its role in normal physiology and development. Moreover, we still do not fully understand how this protein mediates the adverse effects of a variety of environmental pollutants, such as the polycyclic aromatic hydrocarbons (PAHs), the chlorinated dibenzo--dioxins ("dioxins"), and many polyhalogenated biphenyls. To provide a platform for future research, we provide the historical underpinnings of our current state of knowledge about AHR signal transduction, identify a few areas of needed research, and then develop concepts such as adaptive metabolism, ligand structural diversity, and the importance of proligands in receptor activation. We finish with a discussion of the cognate physiological role of the AHR, our perspective on why this receptor is so highly conserved, and how we might think about its cognate ligands in the future.
芳烃受体（AHR）已被研究了近五十年。然而，对于其在正常生理和发育中的作用，我们仍有许多重要问题。此外，我们仍未完全理解该蛋白如何介导多种环境污染物的不良影响，例如多环芳烃（PAHs）、氯代二苯并 - 二恶英（“二恶英”）以及许多多卤代联苯。为了提供一个未来研究的平台，我们阐述了当前关于AHR信号转导知识状态的历史基础，确定了一些需要研究的领域，然后提出了诸如适应性代谢、配体结构多样性以及前体配体在受体激活中的重要性等概念。我们最后讨论了AHR的同源生理作用、我们对于该受体为何高度保守以及未来如何思考其同源配体的观点。
