Abstract

Poly-(ADP)-ribose polymerases (PARPs) are a family of 17 enzymes in humans that have diverse roles in cell physiology including DNA damage repair, transcription, innate immunity, and regulation of signaling pathways. The modular domain architecture of PARPs gives rise to this functional diversity. PARPs catalyze the transfer of ADP-ribose from nicotinamide adenine dinucleotide (NAD⁺) to targets—proteins and poly-nucleic acids. This enigmatic post-translational modification comes in two varieties: the transfer of a single unit of ADP-ribose, known as mono-ADP-ribosylation (MARylation) or the transfer of multiple units of ADP-ribose, known as poly-ADP-ribosylation (PARylation). Emerging data shows that PARPs are regulated at multiple levels to control when and where PARP-mediated M/PARylation occurs in cells. In this review, we will discuss the latest knowledge regarding the regulation of PARPs in cells: from transcription and protein stability to subcellular localization and modulation of catalytic activity.

摘要

聚 (ADP)-核糖聚合酶 (PARP) 是人类 17 种酶的家族，在细胞生理学中具有多种作用，包括 DNA 损伤修复、转录、先天免疫和信号通路调节。PARP 的模块化域架构产生了这种功能多样性。PARPs 催化 ADP-核糖从烟酰胺腺嘌呤二核苷酸 (NAD ⁺) 目标——蛋白质和多核酸。这种神秘的翻译后修饰有两种形式：单个 ADP-核糖单元的转移，称为单 ADP-核糖基化 (MARylation) 或多个 ADP-核糖单元的转移，称为聚 ADP-核糖基化(PARylation)。新出现的数据表明，PARP 在多个层面受到调控，以控制 PARP 介导的 M/PARylation 在细胞中发生的时间和地点。在这篇综述中，我们将讨论有关细胞中 PARPs 调控的最新知识：从转录和蛋白质稳定性到亚细胞定位和催化活性的调节。