Swanson Hollie I
Department of Molecular and Biomedical Pharmacology, University of Kentucky Medical Center, MS 303, Lexington 40536, USA.
Chem Biol Interact. 2002 Sep 20;141(1-2):63-76. doi: 10.1016/s0009-2797(02)00066-2.
Gene activation by the aryl hydrocarbon receptor (AHR) and its DNA binding partner, the aryl hydrocarbon receptor nuclear translocator (ARNT) requires a number of sequential steps that occur following the binding of ligand and entry of the AHR into the nuclear compartment. This includes heterodimerization of the AHR and ARNT, formation of the appropriate amino acid/nucleotide contacts at the GCGTG recognition site and interactions between either the AHR or ARNT with proteins that facilitate changes in chromatin structure. The majority of these steps are likely modulated by changes in both phosphorylation and oxidation status of the AHR, ARNT and associated proteins. Studies of both the basic helix-loop-helix transcription factors and the nuclear hormone receptor family can provide significant insights into how this unique signaling pathway activates its target genes.
芳烃受体(AHR)及其DNA结合伴侣芳烃受体核转运蛋白(ARNT)介导的基因激活需要多个连续步骤,这些步骤在配体结合以及AHR进入细胞核后发生。这包括AHR与ARNT的异源二聚化、在GCGTG识别位点形成适当的氨基酸/核苷酸接触以及AHR或ARNT与促进染色质结构变化的蛋白质之间的相互作用。这些步骤中的大多数可能受到AHR、ARNT及相关蛋白质的磷酸化和氧化状态变化的调节。对碱性螺旋-环-螺旋转录因子和核激素受体家族的研究可以为这一独特的信号通路如何激活其靶基因提供重要见解。