芳香烃受体蛋白质生理功能及在肿瘤中的作用机制  

Physiological Functions of the Aryl Hydrocarbon Receptor and Its Role inTumorigenesis and Development

作　　者：常文静 严汉池 CHANG Wen-Jing;YAN Han-Chi(Laboratory of Structural Biology,School of Life Sciences,Tianjin University,Tianjin 300072,China)

机构地区：[1]天津大学生命科学学院结构生物学实验室,天津300072

出　　处：《中国生物化学与分子生物学报》2024年第1期54-62,共9页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.31870742)资助。

摘　　要：芳香烃受体(aryl hydrocarbon receptor,AHR)作为一种配体依赖性的转录因子,介导2,3,7,8-四氯二苯并对二恶英(2,3,7,8-tetrachloro-dibenzop-dioxin,TCDD)等卤代烃的毒性作用,属于碱性螺旋-环-螺旋-PAS(basic Helix-Loop-Helix-PER-ARNT-SIM,bHLH-PAS)家族成员,具有进化保守性,在多种动物和人类中表达。该蛋白质通过与特定配体结合发生构象改变,转位至细胞核同AHR核转运蛋白(AHR nuclear translocator,ARNT)形成二聚体,并对下游靶基因表达发挥调控作用。最近研究发现,AHR也成为控制细胞增殖分化、凋亡、迁移黏附等多种生理过程的关键转录因子,揭示了AHR在细胞稳态、宿主免疫和肿瘤发展中的重要作用。本文基于国内外对AHR的系列研究,讨论了AHR功能结构、发挥作用的信号通路及其多样性的配体,重点阐述其在防御和屏障保护、调节自身免疫进程、参与调节B细胞和多种T细胞亚群发育分化及其细胞因子的表达,以及在不同微环境中对肿瘤发挥促进或抑制作用的讨论,旨在为相关免疫疾病和肿瘤的AHR靶向治疗提供新思路。The Aryl hydrocarbon receptor(AHR),a ligand-dependent transcription factor,mediates the toxic effects of 2,3,7,8-tetrachloro-dibenzop-dioxin(TCDD)and other halogenated hydrocarbons.It belongs to the basic Helix-Loop-Helix-PER-ARNT-SIM(bHLH-PAS)family.It is evolutionarily conserved and expressed in a variety of animals and humans.The protein undergoes conformational changes by binding to specific ligands and translocates to the nucleus to form a dimer with AHR nuclear translocator(ARNT)to regulate the expression of downstream target genes.Recent studies have found that AHR has also become a key transcription factor controlling various physiological processes such as cell proliferation and differentiation,apoptosis,migration and adhesion,revealing the important role of AHR in cell homeostasis,host immunity and tumor development.Based on a series of studies on AHR,this paper discusses the functional structure of AHR,the signaling pathways,and the diversity of ligands.It focuses on its role in defense and barrier protection,regulation of autoimmune processes,participation in the regulation of the development and differentiation of B cells and various T cell subsets and the expression of cytokines,as well as the promotion or inhibition of tumors in different microenvironments,aiming to provide new ideas for AHR targeted therapy of related immune diseases and tumors.

关 键 词：芳香烃受体 2 3 7 8-四氯二苯并对二恶英 免疫防御 肿瘤 

分 类 号：Q71[生物学—分子生物学]