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Resveratrol and related stilbene-derivatives induce Stress Granules with distinct clearance kinetics
Molecular Biology of the Cell ( IF 3.3 ) Pub Date : 2021-08-25 , DOI: 10.1091/mbc.e21-02-0066
Triana Amen 1 , Anthony Guihur 2 , Christina Zelent 3 , Robertas Ursache 2 , Jörg Wilting 3 , Daniel Kaganovich 1, 4
Affiliation  

Stress Granules are ribonucleoprotein functional condensates that form during stress conditions in all eukaryotic cells. Although their stress-survival function is far from clear, Stress Granules have been implicated in the regulation of many vital cellular pathways. Consequently, SG dysfunction is thought to be a mechanistic point of origin for many neurodegenerative disorders, including Amyotrophic Lateral Sclerosis (ALS). Additionally, SGs are thought to play a role in pathogenic pathways as diverse as viral infection and chemotherapy resistance. There is a growing consensus around the hypothesis that understanding the mechanistic regulation of SG physical properties is essential to understanding their function. Although the internal dynamics and condensation mechanisms of SGs have been broadly investigated, there have been fewer investigations into the timing of SG formation and clearance in live cells. Since the lifetime of SG persistence can be a key factor in their function and tendency towards pathological dysregulation, SG clearance mechanisms deserve particular attention. Here we show that resveratrol and its analogues, piceatannol, pterostilbene, and 3,4,5,4′ tetramethoxystilbene induce G3BP-dependent SG formation with atypically rapid clearance kinetics. Resveratrol binds to G3BP, thereby reducing its protein-protein association valency. We suggest that altering G3BP valency is a pathway for the formation of uniquely transient SGs.



中文翻译:

白藜芦醇和相关的芪衍生物诱导具有不同清除动力学的应激颗粒

应激颗粒是在所有真核细胞的应激条件下形成的核糖核蛋白功能性缩合物。尽管它们的应激生存功能远未明确,但应激颗粒与许多重要细胞途径的调节有关。因此,SG 功能障碍被认为是许多神经退行性疾病的机制起源点,包括肌萎缩侧索硬化症 (ALS)。此外,SGs 被认为在病毒感染和化疗耐药等多种致病途径中发挥作用。关于理解 SG 物理特性的机械调节对于理解其功能至关重要的假设越来越达成共识。尽管已经广泛研究了 SG 的内部动力学和凝聚机制,对活细胞中 SG 形成和清除时间的研究较少。由于 SG 持久性的寿命可能是其功能和病理失调趋势的关键因素,因此 SG 清除机制值得特别关注。在这里,我们表明白藜芦醇及其类似物、白杉醇、紫檀芪和 3,4,5,4' 四甲氧基芪诱导 G3BP 依赖性 SG 形成,具有非典型的快速清除动力学。白藜芦醇与 G3BP 结合,从而降低其蛋白质-蛋白质结合价。我们建议改变 G3BP 价是形成独特瞬态 SG 的途径。SG 清除机制值得特别关注。在这里,我们表明白藜芦醇及其类似物、白杉醇、紫檀芪和 3,4,5,4' 四甲氧基芪诱导 G3BP 依赖性 SG 形成,具有非典型的快速清除动力学。白藜芦醇与 G3BP 结合,从而降低其蛋白质-蛋白质结合价。我们建议改变 G3BP 价是形成独特瞬态 SG 的途径。SG 清除机制值得特别关注。在这里,我们表明白藜芦醇及其类似物、白杉醇、紫檀芪和 3,4,5,4' 四甲氧基芪诱导 G3BP 依赖性 SG 形成,具有非典型的快速清除动力学。白藜芦醇与 G3BP 结合,从而降低其蛋白质-蛋白质结合价。我们建议改变 G3BP 价是形成独特瞬态 SG 的途径。

更新日期:2021-08-26
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