Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR, USA.
Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR, USA.
Trends Biochem Sci. 2022 May;47(5):390-402. doi: 10.1016/j.tibs.2021.07.002. Epub 2021 Aug 5.
Poly-ADP-ribose-polymerases (PARPs) are a family of 17 enzymes that regulate a diverse range of cellular processes in mammalian cells. PARPs catalyze the transfer of ADP-ribose from NAD to target molecules, most prominently amino acids on protein substrates, in a process known as ADP-ribosylation. Identifying the direct protein substrates of individual PARP family members is an essential first step for elucidating the mechanism by which PARPs regulate a particular pathway in cells. Two distinct chemical genetic (CG) strategies have been developed for identifying the direct protein substrates of individual PARP family members. In this review, we discuss the design principles behind these two strategies and how target identification has provided novel insight into the cellular function of individual PARPs and PARP-mediated ADP-ribosylation.
聚 ADP-核糖聚合酶（PARPs）是一个家族的 17 种酶，在哺乳动物细胞中调节多种细胞过程。PARPs 催化 NAD 中的 ADP-核糖转移到靶分子，最常见的是蛋白质底物上的氨基酸，这一过程称为 ADP-核糖基化。鉴定个体 PARP 家族成员的直接蛋白质底物是阐明 PARPs 调节细胞中特定途径的机制的重要第一步。已经开发了两种不同的化学遗传（CG）策略来鉴定个体 PARP 家族成员的直接蛋白质底物。在这篇综述中，我们讨论了这两种策略背后的设计原则，以及靶标鉴定如何为个体 PARPs 和 PARP 介导的 ADP-核糖基化的细胞功能提供新的见解。
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