1 Institute of Protein Biochemistry, National Research Council , Via Pietro Castellino 111, 80131 Naples , Italy.
2 Division of Molecular Biology, Ruđer Bošković Institute , Bijenička cesta 54, 10000 Zagreb , Croatia.
Open Biol. 2019 Apr 26;9(4):190041. doi: 10.1098/rsob.190041.
ADP-ribosylation (ADPr) is a reversible post-translational modification of proteins, which controls major cellular and biological processes, including DNA damage repair, cell proliferation and differentiation, metabolism, stress and immune responses. In order to maintain the cellular homeostasis, diverse ADP-ribosyl transferases and hydrolases are involved in the fine-tuning of ADPr systems. The control of ADPr network is vital, and dysregulation of enzymes involved in the regulation of ADPr signalling has been linked to a number of inherited and acquired human diseases, such as several neurological disorders and in cancer. Conversely, the therapeutic manipulation of ADPr has been shown to ameliorate several disorders in both human and animal models. These include cardiovascular, inflammatory, autoimmune and neurological disorders. Herein, we summarize the recent findings in the field of ADPr, which support the impact of this modification in human pathophysiology and highlight the curative potential of targeting ADPr for translational and molecular medicine.
ADP-核糖基化(ADPr)是蛋白质的一种可逆翻译后修饰,可调控多种重要的细胞和生物学过程,包括 DNA 损伤修复、细胞增殖和分化、代谢、应激和免疫反应等。为了维持细胞内稳态,多种 ADP-核糖基转移酶和水解酶参与 ADPr 系统的精细调控。ADPr 网络的调控至关重要,参与 ADPr 信号调控的酶的失调与多种遗传性和获得性人类疾病相关,如多种神经退行性疾病和癌症。相反,ADPr 的治疗性操作已被证明可以改善人类和动物模型中的多种疾病。这些疾病包括心血管疾病、炎症性疾病、自身免疫性疾病和神经退行性疾病等。在此,我们总结了 ADPr 领域的最新研究发现,这些发现支持了这种修饰在人类病理生理学中的作用,并强调了针对 ADPr 的治疗方法在转化医学和分子医学中的潜在应用价值。