ADP-ribosylation: from molecular mechanisms to human disease

Abstract Post-translational modification of proteins by ADP-ribosylation, catalysed by poly (ADP-ribose) polymerases (PARPs) using NAD+ as a substrate, plays central roles in DNA damage signalling and repair, modulates a range of cellular signalling cascades and initiates programmed cell death by parthanatos. Here, we present mechanistic aspects of ADP-ribose modification, PARP activation and the cellular functions of ADP-ribose signalling, and discuss how this knowledge is uncovering therapeutic avenues for the treatment of increasingly prevalent human diseases such as cancer, ischaemic damage and neurodegeneration.摘要：由多聚ADP核糖聚合酶（poly(ADP-ribose) polymerases, PARPs）以烟酰胺腺嘌呤二核苷酸（NAD+）作为底物催化的蛋白质ADP核糖基化（ADP-ribosylation）翻译后修饰，在DNA损伤信号传导与修复中发挥核心作用，调控多条细胞信号级联反应，并通过副凋亡（parthanatos）启动程序性细胞死亡。本文阐述了ADP核糖基化修饰的机制、PARP的激活过程以及ADP核糖信号传导的细胞功能，并探讨了该领域研究如何为癌症、缺血性损伤与神经退行性疾病等日益高发的人类疾病的治疗发掘全新的治疗途径。