The Landscape of AhR Regulators and Coregulators to Fine-Tune AhR Functions.

The Landscape of AhR Regulators and Coregulators to Fine-Tune AhR Functions.
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AhR监管机构和合作监管机构对AhR职能进行微调的前景。

DOI:
10.3390/ijms22020757
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发表时间:
2021-01-13
影响因子:
5.6
通讯作者:
Fallarino F
Fallarino F
中科院分区:
生物学2区
文献类型:
--
作者:
Gargaro M;Scalisi G;Manni G;Mondanelli G;Grohmann U;Fallarino F

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芳香烃受体(AhR)是一种配体激活的转录因子,介导许多细胞反应。AhR最初是在毒理学中研究的,因为它能够结合环境污染物,在过去的20年里,AhR在免疫学领域引起了极大的关注。此外,内源性和植物源性配体的发现表明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,其可以在感测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,几个因素似乎有助于基因转录调节AhR的结果,包括配体本身的性质和AhR诱导的酶,局部组织微环境,以及细胞中存在的辅助调节因子或特定的转录因子的进一步代谢。在这里,我们回顾了目前的知识阵列上的转录因子和辅助调节,通过与AhR相互作用,调整其转录活性响应内源性和外源性配体。
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.
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