聚（ADP-核糖）聚合酶 1 功能的翻译后修饰调节。

Regulation of poly(ADP-Ribose) polymerase 1 functions by post-translational modifications.

机构信息

Institute of Bioinformatics and Medical Engineering, Jiangsu University of Technology, Changzhou 213001, China.

Division of Molecular Modification and Cancer Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 Japan.

出版信息

Front Biosci (Landmark Ed). 2018 Jan 1;23(1):13-26. doi: 10.2741/4578.

DOI:10.2741/4578

PMID:28930534

Abstract

The poly(ADP-ribose) polymerases (PARPs) catalyze poly(ADP-ribosyl)ation, a post-translational modification of proteins. This consists of the attachment of mono- or poly- (ADP)-ribose units from nicotinamide adenine dinucleotide (NAD) to specific polar residues of target proteins. PARP1 is the most abundant and best-characterized member of the family of PARP enzymes. PARP1 plays key roles in DNA repair, as well as a wide variety of cellular processes, including transcriptional regulation, chromatin modulation, cellular signaling pathway, inflammation, cellular stress responses and so on. Hence, PARP1 inhibitors have become a promising therapeutic approach for human diseases including cancer. Recent studies indicate that post-translational modifications (PTMs) such as phosphorylation, acetylation, and methylation are crucial for the regulation of PARP1 activity, and dysregulation of modifications on PARP1 is observed in human cancer. In this review, we describe the importance of PTMs to regulate the activity of PARP1, and the involvement of dysregulation of PTMs in human cancer.

摘要

多聚（ADP-核糖）聚合酶（PARPs）催化多聚（ADP-核糖）化，这是一种蛋白质的翻译后修饰。它包括从烟酰胺腺嘌呤二核苷酸（NAD）将单聚或多聚（ADP）-核糖单元附着到靶蛋白的特定极性残基上。PARP1 是 PARP 酶家族中最丰富和研究最透彻的成员。PARP1 在 DNA 修复以及广泛的细胞过程中发挥关键作用，包括转录调控、染色质调节、细胞信号通路、炎症、细胞应激反应等。因此，PARP1 抑制剂已成为治疗人类疾病（包括癌症）的一种有前途的方法。最近的研究表明，翻译后修饰（PTMs），如磷酸化、乙酰化和甲基化，对 PARP1 活性的调节至关重要，并且在人类癌症中观察到 PARP1 上修饰的失调。在这篇综述中，我们描述了 PTMs 对调节 PARP1 活性的重要性，以及 PTMs 失调在人类癌症中的参与。