Exactly the Same but Different: Promiscuity and Diversity in the Molecular Mechanisms of Action of the Aryl Hydrocarbon (Dioxin) Receptor
Exactly the Same but Different: Promiscuity and Diversity in the Molecular Mechanisms of Action of the Aryl Hydrocarbon (Dioxin) Receptor
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DOI：
10.1093/toxsci/kfr218
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发表时间：
2011-11-01
影响因子：
3.8
通讯作者：
Zhao, Bin
中科院分区：
文献类型：
--
作者：
Denison, Michael S.;Soshilov, Anatoly A.;Zhao, Bin
Ah受体（AhR）是一种配体依赖性转录因子，介导广泛的生物学和毒理学效应，这些效应是由于暴露于结构多样的各种合成和天然存在的化学品而产生的。尽管AhR的总体作用机制已经被广泛研究并且涉及经典的核受体作用机制（即，配体依赖性核定位、蛋白质异源二聚化、配体受体作为蛋白质复合物与其特异性DNA识别序列的结合和基因表达的激活），通常缺乏导致大多数AhR依赖性生化、生理和毒理学效应的确切分子事件的细节。正在进行的研究工作继续描述一个不断扩大的名单配体，物种和组织特异性光谱的AhR依赖的生物和毒理学效应，似乎增加了更多的复杂性的机制。然而，与此同时，这些研究也在确定和表征AhR发挥作用的新途径和分子机制，并在内源性发育和生理途径以及对外源性化学物质的反应中发挥关键调节作用。在这里，我们提供了一个概述的经典和非经典的机制，可以有助于在人类和其他物种中观察到的配体依赖性激活的AhR信号转导通路的反应的差异敏感性和多样性。
The Ah receptor (AhR) is a ligand-dependent transcription factor that mediates a wide range of biological and toxicological effects that result from exposure to a structurally diverse variety of synthetic and naturally occurring chemicals. Although the overall mechanism of action of the AhR has been extensively studied and involves a classical nuclear receptor mechanism of action (i.e., ligand-dependent nuclear localization, protein heterodimerization, binding of liganded receptor as a protein complex to its specific DNA recognition sequence and activation of gene expression), details of the exact molecular events that result in most AhR-dependent biochemical, physiological, and toxicological effects are generally lacking. Ongoing research efforts continue to describe an ever-expanding list of ligand-, species-, and tissue-specific spectrum of AhR-dependent biological and toxicological effects that seemingly add even more complexity to the mechanism. However, at the same time, these studies are also identifying and characterizing new pathways and molecular mechanisms by which the AhR exerts its actions and plays key modulatory roles in both endogenous developmental and physiological pathways and response to exogenous chemicals. Here we provide an overview of the classical and nonclassical mechanisms that can contribute to the differential sensitivity and diversity in responses observed in humans and other species following ligand-dependent activation of the AhR signal transduction pathway.