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首页> 外文期刊>The European Journal of Neuroscience >Mechanisms of circadian clock interactions with aryl hydrocarbon receptor signalling
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Mechanisms of circadian clock interactions with aryl hydrocarbon receptor signalling

机译：与芳烃受体信号传导的昼夜节律相互作用的机制

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摘要

Per-Arnt-Sim (PAS) domain-containing proteins are critical to homeostatic regulatory networks that mediate responsiveness to environmental change. PAS domains are multifunctional structural motifs that allow protein-protein interactions amongst family members, typically forming heterodimeric transcription factors to affect the transcription of target genes. Prototypical PAS domain-dependent pathways include the circadian clock network and metabolic regulation of the xenobiotic response through the aryl hydrocarbon receptor (AhR). Both pathways are increasingly linked to health, and alteration in their function contributes to development of disease. The AhR demonstrates promiscuity in ligand binding and selectivity during heterodimer formation, which allows varied combinations of protein-protein interactions with other Per-Arnt-Sim (PAS) domain-containing proteins and crosstalk amongst signalling pathways, including the molecular clockworks. AhR and the circadian signalling pathways are highly integrated and reciprocally regulated. AhR exhibits a rhythmic expression and time-dependent sensitivity to activation by AhR agonists. Conversely, AhR influences amplitude and phase of rhythms in circadian clock genes, hormones, and behaviour. Understanding the molecular interactions between AhR and the clock provides insight into physiological regulation of rhythmic processes and provides an innovative approach to development of therapeutics.
机译：含有含有域的含域域的蛋白质对稳态监管网络至关重要，使对环境变化的反应性讨论。 PAS结构域是多功能的结构基质，其允许家庭成员之间的蛋白质 - 蛋白质相互作用，通常形成异二聚体转录因子以影响靶基因的转录。原型PAS域依赖性途径包括昼夜节律钟网络和通过芳芳烃受体（AHR）的异骨响应的代谢调节。两种途径与健康越来越联系，其功能的改变有助于疾病的发展。 AHR在异二聚体形成期间阐述了配体结合和选择性的滥用，这允许在信号通路中的含有蛋白质 - 蛋白质相互作用与含有分子筒点的信号通路中的其他含量域域的蛋白质和串扰组合。 AHR和昼夜信令途径高度集成和互动调节。 AHR表现出节奏的表达和时间依赖性敏感性对AHR激动剂的激活。相反，AHR影响昼夜钟表基因，激素和行为中节奏的幅度和阶段。了解AHR和时钟之间的分子相互作用提供了对节律过程的生理调节的洞察力，并为治疗方法提供了一种创新的发展方法。

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