多聚（ADP-核糖）：生物分子凝聚物形成的动态触发因子。
Poly(ADP-ribose): A Dynamic Trigger for Biomolecular Condensate Formation.
机构信息
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Molecular Biology and Genetics, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
出版信息
Trends Cell Biol. 2020 May;30(5):370-383. doi: 10.1016/j.tcb.2020.02.002. Epub 2020 Feb 20.
Poly(ADP-ribose) (PAR) is a nucleic acid-like protein modification that can seed the formation of microscopically visible cellular compartments that lack enveloping membranes, recently termed biomolecular condensates. These PAR-mediated condensates are linked to cancer, viral infection, and neurodegeneration. Recent data have shown the therapeutic potential of modulating PAR conjugation (PARylation): PAR polymerase (PARP) inhibitors can modulate the formation and dynamics of these condensates as well as the trafficking of their components - many of which are key disease factors. However, the way in which PARylation facilitates these functions remains unclear, partly because of our lack of understanding of the fundamental parameters of intracellular PARylation, including the sites that are conjugated, PAR chain length and structure, and the physicochemical properties of the conjugates. This review first introduces the role of PARylation in regulating biomolecular condensates, followed by discussion of current knowledge gaps, potential solutions, and therapeutic applications.
多聚（ADP-核糖）（PAR）是一种类似核酸的蛋白质修饰物，可作为种子诱导形成缺乏包膜的微观可见细胞区室，最近被称为生物分子凝聚物。这些由 PAR 介导的凝聚物与癌症、病毒感染和神经退行性变有关。最近的数据表明，调节 PAR 连接（PARylation）具有治疗潜力：PAR 聚合酶（PARP）抑制剂可调节这些凝聚物的形成和动态以及它们成分的运输——其中许多是关键的疾病因素。然而，PARylation 促进这些功能的方式仍不清楚，部分原因是我们对细胞内 PARylation 的基本参数缺乏了解，包括连接的位点、PAR 链长和结构以及共轭物的物理化学性质。这篇综述首先介绍了 PARylation 在调节生物分子凝聚物中的作用，然后讨论了当前的知识空白、潜在的解决方案和治疗应用。
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