细胞内AhR信号转导通路的机制研究

Biological Role of AhR Signaling Pathway

芳香族化合物受体((Aryl hydrocarbon receptor,AhR)是一个属于碱性螺旋-环-螺旋(basichelix-loop-helix(bHLH))Per-Arnt-Sim同源域(Per-Arnt-Sim homology domain(PAS))家族的转录因子。在外界环境激素2,3,7,8-四氯-二苯并-对-二恶英(2,3,7,8-tetrachlorodibenzo-p-dioxin,2,3,7,8-TCDD)的刺激下,AhR从细胞质中转运入细胞核中,与另一个蛋白AhR核转运蛋白(AhR nuclear transportor,ARNT)结合,形成异二聚体,结合在下游靶基因上,使相应基因,如细胞色素(cytochrome P450 1A1/cytochrome P450 1B1,CYP1A1/CYP1B1)等异常表达,从而干扰动物的内分泌,引起免疫毒性,甚至导致癌症的发生。AhR的激活过程,涉及多种蛋白修饰的变化,如磷酸化、泛素化等,这些修饰调控了蛋白的定位、活性、稳定性等。AhR信号转导通路,与其他的很多通路,如E2-ER,MAPK通路等相互交叉。本文旨在描述细胞内AhR通路的激活过程,功能,以及与其他通路之间相互的调控作用,以期为TCDD引发的相关疾病的预防和治疗提供思路。

AhR（Aryl hydrocarbon receptor） is a transcription factor belongs to the basic helix-loop-helix（bHLH） Per-Arnt-Sim homology domain（PAS） family.When binds with the ligand 2,3,7,8-TCDD（2,3,7,8-tetrachlorodibenzo-p-dioxin）,AhR is activated and translocates from cytoplasm to nuclear,forming heterodimer with ARNT（AhR nuclear transportor） and binding to DNA elements and leading to abnormal expression of the target genes such as CYP1A1/CYP1B1（cytochrome P450 1A1/cytochrome P450 1B1）,which finally causes several diseases including cancer.There are several modifications during the activation of AhR,including phosphorylation and ubiquitination and so on,which are related to the localization,activity and stability of proteins.AhR signal pathway also cross-talks with E2-ER and MAPK pathways.This article aims to describe the activation and functions of AhR,and the interactions with other pathways,hoping to give insights into the prevention and therapy of diseases caused by TCDD.