Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy.
Int J Mol Sci. 2021 Jan 13;22(2):757. doi: 10.3390/ijms22020757.
The aryl-hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates numerous cellular responses. Originally investigated in toxicology because of its ability to bind environmental contaminants, AhR has attracted enormous attention in the field of immunology in the last 20 years. In addition, the discovery of endogenous and plant-derived ligands points to AhR also having a crucial role in normal cell physiology. Thus, AhR is emerging as a promiscuous receptor that can mediate either toxic or physiologic effects upon sensing multiple exogenous and endogenous molecules. Within this scenario, several factors appear to contribute to the outcome of gene transcriptional regulation by AhR, including the nature of the ligand as such and its further metabolism by AhR-induced enzymes, the local tissue microenvironment, and the presence of coregulators or specific transcription factors in the cell. Here, we review the current knowledge on the array of transcription factors and coregulators that, by interacting with AhR, tune its transcriptional activity in response to endogenous and exogenous ligands.
芳香烃受体 (AhR) 是一种配体激活的转录因子，可介导多种细胞反应。由于其能够结合环境污染物，最初在毒理学中进行了研究，而在过去的 20 年中，AhR 在免疫学领域引起了极大的关注。此外，内源性和植物衍生配体的发现表明 AhR 在正常细胞生理学中也具有至关重要的作用。因此，AhR 作为一种混杂受体出现，能够在感知多种外源性和内源性分子时介导毒性或生理效应。在这种情况下，似乎有几个因素会影响 AhR 对基因转录调控的结果，包括配体本身的性质及其被 AhR 诱导的酶进一步代谢、局部组织微环境以及细胞中存在的共调节剂或特定转录因子。在这里，我们综述了目前关于转录因子和共调节剂的知识，这些转录因子和共调节剂通过与 AhR 相互作用，根据内源性和外源性配体调节其转录活性。
