The poly(ADP-ribose) polymerase (PARP) family constitutes a major group of proteins and enzymes essential for the maintenance of cellular homeostasis under physiological conditions and plays a pivotal role in the onset and progression of multiple pathological states. Members of the PARP family are classified into distinct subgroups based on their subcellular localization, structural organization, and ADP-ribosyltransferase activity. To date, the majority of studies have focused on DNA-dependent PARPs, owing to their well-established involvement in DNA repair mechanisms, cell cycle regulation, and diverse human pathologies. Nevertheless, over the past decade, a smaller subset of PARPs—limited in both abundance and enzymatic activity—has emerged as a critical regulator of numerous cellular processes, including embryonic development and disease progression. Within this subset, mono(ADP-ribosyl) transferases (MARTs) have gained growing attention as potential therapeutic targets in cancer, cardiovascular disorders, and neurodegenerative diseases. The ADP-ribose (ADPr) cycle, which comprises both branched poly(ADP-ribose) (PAR) polymers and mono-ADP-ribose moieties present either in free form or covalently bound to cellular substrates, is tightly regulated to ensure cellular homeostasis. This regulation relies on a finely tuned balance between ADP-ribosylation, DePARylation, and the subsequent recycling of mono-ADP-ribose. In this review, we provide a comprehensive overview of the biological roles of mono-ADP-ribosylation (MARylation) and DePARylation, with particular emphasis on their contribution to cancer-related processes. In addition, we discuss emerging evidence supporting their translational relevance and therapeutic potential. In conclusion, MARylation and DePARylation represent two increasingly recognized regulatory pathways whose expanding clinical significance highlights the need for deeper mechanistic understanding and further exploration in both basic and translational research.
聚腺苷二磷酸核糖聚合酶（PARP）家族是一类重要的蛋白质与酶类，在生理条件下对维持细胞稳态至关重要，并在多种病理状态的发生与发展中发挥关键作用。根据亚细胞定位、结构组成及ADP-核糖基转移酶活性的差异，PARP家族成员被划分为不同亚群。迄今为止，大多数研究集中于DNA依赖性PARPs，因其在DNA修复机制、细胞周期调控及多种人类疾病中的作用已得到充分证实。然而在过去十年中，一个数量较少且酶活性有限的PARPs亚群逐渐被发现，它们作为胚胎发育和疾病进展等众多细胞过程的关键调控因子而备受关注。其中，单ADP-核糖基转移酶（MARTs）作为癌症、心血管疾病和神经退行性疾病的潜在治疗靶点日益受到重视。由分支状聚ADP-核糖（PAR）聚合物以及以游离形式或共价结合于细胞底物的单ADP-核糖单元构成的ADP-核糖（ADPr）循环受到精密调控，以维持细胞稳态。这种调控依赖于ADP-核糖基化、去ADP-核糖基化以及后续单ADP-核糖循环之间微妙的动态平衡。本文系统综述了单ADP-核糖基化（MARylation）与去ADP-核糖基化（DePARylation）的生物学功能，重点探讨其在癌症相关进程中的作用机制。同时，我们讨论了支持其转化医学价值与治疗潜力的新兴证据。综上所述，MARylation与DePARylation作为两条日益受关注的调控通路，其不断拓展的临床意义凸显了在基础与转化研究领域深化机制认知和持续探索的必要性。
Targeting MARylation and DePARylation in Cancer Therapy: New Promising Therapeutic Opportunities
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