ADP-ribose hydrolases: biological functions and potential therapeutic targets.

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jingpeng Wang, Zhao-Qi Wang, Wen Zong
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引用次数: 0

Abstract

ADP-ribosylation (ADPRylation), which encompasses poly(ADP-ribosyl)ation and mono(ADP-ribosyl)ation, is an important post-translational modification catalysed by the poly(ADP-ribose) polymerase (PARP) enzyme superfamily. The process involves writers (PARPs) and erasers (ADP-ribose hydrolases), which work together to precisely regulate diverse cellular and molecular responses. Although the PARP-mediated synthesis of ADP-ribose (ADPr) has been well studied, ADPr degradation by degrading enzymes deserves further investigation. Nonetheless, recent studies have provided important new insights into the biology and functions of ADPr hydrolases. Notably, research has illuminated the significance of the poly(ADP-ribose) degradation pathway and its activation by the coordinated actions of poly(ADP-ribose) glycohydrolase and other ADPr hydrolases, which have been identified as key components of ADPRylation signalling networks. The degradation pathway has been proposed to play crucial roles in key cellular processes, such as DNA damage repair, chromatin dynamics, transcriptional regulation and cell death. A deep understanding of these ADPr erasing enzymes provides insights into the biological roles of ADPRylation in human health and disease aetiology and paves the road for the development of novel therapeutic strategies. This review article provides a summary of current knowledge about the biochemical and molecular functions of ADPr erasers and their physiological implications in human pathology.

ADP 核糖水解酶:生物功能和潜在治疗靶点。
ADP-ribosylation (ADPRylation) 包括多(ADP-ribosyl)聚合和单(ADP-ribosyl)聚合,是由多(ADP-ribose)聚合酶(PARP)超家族催化的一种重要的翻译后修饰。这一过程涉及写入者(PARPs)和擦除者(ADP-核糖水解酶),它们共同作用,精确调节各种细胞和分子反应。尽管 PARP 介导的 ADP-ribose(ADPr)合成过程已得到深入研究,但降解酶对 ADPr 的降解作用仍值得进一步研究。不过,最近的研究为了解 ADPr 水解酶的生物学特性和功能提供了重要的新见解。值得注意的是,研究揭示了多(ADP-核糖)降解途径的重要性,以及多(ADP-核糖)糖水解酶和其他 ADPr 水解酶协调作用激活该途径的情况,这些酶已被确定为 ADPRylation 信号网络的关键组成部分。降解途径被认为在 DNA 损伤修复、染色质动力学、转录调控和细胞死亡等关键细胞过程中发挥着至关重要的作用。深入了解这些 ADPr 侵蚀酶有助于深入了解 ADPRylation 在人类健康和疾病病因学中的生物学作用,并为开发新型治疗策略铺平道路。这篇综述文章概述了目前有关 ADPr 侵蚀酶的生化和分子功能及其在人类病理学中的生理意义的知识。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Expert Reviews in Molecular Medicine
Expert Reviews in Molecular Medicine BIOCHEMISTRY & MOLECULAR BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
7.40
自引率
1.60%
发文量
45
期刊介绍: Expert Reviews in Molecular Medicine is an innovative online journal featuring authoritative and timely Reviews covering gene therapy, immunotherapeutics, drug design, vaccines, genetic testing, pathogenesis, microbiology, genomics, molecular epidemiology and diagnostic techniques. We especially welcome reviews on translational aspects of molecular medicine, particularly those related to the application of new understanding of the molecular basis of disease to experimental medicine and clinical practice.
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