PDF(Pubmed)
Abstract：
Glucocorticoids (GCs) are hormones involved in circadian adaptation and stress response, and it is also noteworthy that these steroidal molecules present potent anti-inflammatory action through GC receptors (GR). Upon ligand-mediated activation, GR translocates to the nucleus, and regulates gene expression related to metabolism, acute-phase response and innate immune response. GR field of research has evolved considerably in the last decades, providing varied mechanisms that contributed to the understanding of transcriptional regulation and also impacted drug design for treating inflammatory diseases. Liquid-liquid phase separation (LLPS) in cellular processes represents a recent topic in biology that conceptualizes membraneless organelles and microenvironments that promote, or inhibit, chemical reactions and interactions of protein or nucleic acids. The formation of these molecular condensates has been implicated in gene expression control, and recent evidence shows that GR and other steroid receptors can nucleate phase separation (PS). Here we briefly review the varied mechanisms of transcriptional control by GR, which are largely studied in the context of inflammation, and further present how PS can be involved in the control of gene expression. Lastly, we consider how the reported advances on LLPS during transcription control, specially for steroid hormone receptors, could impact the different modalities of GR action on gene expression, adding a new plausible molecular event in glucocorticoid signal transduction.
摘要：
糖皮质激素（GC）是参与昼夜节律适应和应激反应的激素，并且还值得注意的是,这些甾体分子通过GC受体(GR)表现出有效的抗炎作用。在配体介导的激活后，GR易位到细胞核,调节与代谢相关的基因表达，急性期反应和先天免疫反应。GR的研究领域在过去的几十年里有了很大的发展，提供多种机制，有助于理解转录调控，也影响治疗炎性疾病的药物设计。细胞过程中的液-液相分离（LLPS）代表了生物学中的一个最新主题，该主题将无膜细胞器和微环境概念化，或抑制，蛋白质或核酸的化学反应和相互作用。这些分子缩合物的形成与基因表达控制有关，和最近的证据表明，GR和其他类固醇受体可以成核相分离（PS）。在这里，我们简要回顾了GR转录控制的各种机制，这些研究主要是在炎症的背景下进行的，并进一步介绍了PS如何参与基因表达的控制。最后,我们考虑在转录控制过程中LLPS的报道进展，特别是类固醇激素受体，可能会影响不同的GR作用方式对基因表达的影响，在糖皮质激素信号转导中增加了一个新的可信分子事件。
