Poly(ADP-ribose)-dependent ubiquitination and its clinical implications.
Poly(ADP-ribose)-dependent ubiquitination and its clinical implications.
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DOI：
10.1016/j.bcp.2019.05.006
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发表时间：
2019-05
影响因子：
5.8
通讯作者：
Christina A. Vivelo;V. Ayyappan;A. Leung
中科院分区：
文献类型：
--
作者：
Christina A. Vivelo;V. Ayyappan;A. Leung
ADP-核糖化-将一个或多个ADP-核糖单位添加到蛋白质上-是一种具有治疗意义的翻译后修饰，与癌症、神经变性和感染性疾病有关。蛋白质修饰调控广泛的生物过程，包括DNA修复、转录、RNA代谢和非膜性结构的结构完整性。ADP-核糖的聚合形式聚(ADP-核糖)最近被认为是通过泛素-蛋白酶体系统触发蛋白质降解的信号。利用信息学分析，我们发现这些泛素化的底物往往是低丰度的蛋白质，这可能是信号网络或代谢过程中的限速因子。在这篇综述中，我们综述了目前文献中关于聚(ADP-核糖)依赖的泛素化(PADU)的生物学机制、底物及其与疾病的相关性。
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.