Mikolčević Petra, Hloušek-Kasun Andrea, Ahel Ivan, Mikoč Andreja
Division of Molecular Biology, Ruđer Bošković Institute, Zagreb, Croatia.
Sir William Dunn School of Pathology, University of Oxford, UK.
Comput Struct Biotechnol J. 2021 Apr 17;19:2366-2383. doi: 10.1016/j.csbj.2021.04.023. eCollection 2021.
ADP-ribosylation is an ancient posttranslational modification present in all kingdoms of life. The system likely originated in bacteria where it functions in inter- and intra-species conflict, stress response and pathogenicity. It was repeatedly adopted via lateral transfer by eukaryotes, including humans, where it has a pivotal role in epigenetics, DNA-damage repair, apoptosis, and other crucial pathways including the immune response to pathogenic bacteria and viruses. In other words, the same ammunition used by pathogens is adapted by eukaryotes to fight back. While we know quite a lot about the eukaryotic system, expanding rather patchy knowledge on bacterial and viral ADP-ribosylation would give us not only a better understanding of the system as a whole but a fighting advantage in this constant arms race. By writing this review we hope to put into focus the available information and give a perspective on how this system works and can be exploited in the search for therapeutic targets in the future. The relevance of the subject is especially highlighted by the current situation of being amid the world pandemic caused by a virus harbouring and dependent on a representative of such a system.
ADP核糖基化是一种古老的翻译后修饰,存在于所有生物界。该系统可能起源于细菌,在种间和种内冲突、应激反应和致病性中发挥作用。它通过横向转移被包括人类在内的真核生物反复采用,在表观遗传学、DNA损伤修复、细胞凋亡以及其他关键途径(包括对病原菌和病毒的免疫反应)中起关键作用。换句话说,病原体使用的相同“武器”被真核生物用来反击。虽然我们对真核生物系统了解很多,但扩充关于细菌和病毒ADP核糖基化的零散知识,不仅能让我们更好地理解整个系统,还能在这场持续的军备竞赛中获得战斗优势。通过撰写本综述,我们希望聚焦现有信息,并就该系统如何运作以及未来如何用于寻找治疗靶点给出一个观点。由于当前处于由一种携带并依赖此类系统代表的病毒引发的全球大流行之中,该主题的相关性尤其突出。