聚（ADP-核糖）依赖性泛素化及其临床意义。
Poly(ADP-ribose)-dependent ubiquitination and its clinical implications.
机构信息
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
出版信息
Biochem Pharmacol. 2019 Sep;167:3-12. doi: 10.1016/j.bcp.2019.05.006. Epub 2019 May 8.
Abstract
ADP-ribosylation-the addition of one or multiple ADP-ribose units onto proteins-is a therapeutically important post-translational modification implicated in cancer, neurodegeneration, and infectious diseases. The protein modification regulates a broad range of biological processes, including DNA repair, transcription, RNA metabolism, and the structural integrity of nonmembranous structures. The polymeric form of ADP-ribose, poly(ADP-ribose), was recently identified as a signal for triggering protein degradation through the ubiquitin-proteasome system. Using informatics analyses, we found that these ubiquitinated substrates tend to be low abundance proteins, which may serve as rate-limiting factors within signaling networks or metabolic processes. In this review, we summarize the current literature on poly(ADP-ribose)-dependent ubiquitination (PARdU) regarding its biological mechanisms, substrates, and relevance to diseases.
摘要
ADP-核糖基化-将一个或多个 ADP-核糖单位添加到蛋白质上-是一种治疗上重要的翻译后修饰，与癌症、神经退行性疾病和传染病有关。蛋白质修饰调节广泛的生物过程，包括 DNA 修复、转录、RNA 代谢和非膜结构的结构完整性。ADP-核糖的聚合形式，多聚（ADP-核糖），最近被确定为通过泛素-蛋白酶体系统触发蛋白质降解的信号。使用信息学分析，我们发现这些泛素化的底物往往是低丰度的蛋白质，它们可能作为信号网络或代谢过程中的限速因素。在这篇综述中，我们总结了关于多聚（ADP-核糖）依赖性泛素化（PARdU）的当前文献，包括其生物学机制、底物及其与疾病的相关性。
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