Abstract：
Modification of proteins by ADP-ribose (PARsylation) is catalyzed by the poly(ADP-ribose) polymerase (PARP) family of enzymes exemplified by PARP1, which controls chromatin organization and DNA repair. Additionally, PARsylation induces ubiquitylation and proteasomal degradation of its substrates because PARsylation creates a recognition site for E3-ubiquitin ligase. The steady-state levels of the adaptor protein SH3-domain binding protein 2 (3BP2) is negatively regulated by tankyrase (PARP5), which coordinates ubiquitylation of 3BP2 by the E3-ligase ring finger protein 146 (RNF146). 3BP2 missense mutations uncouple 3BP2 from tankyrase-mediated negative regulation and cause Cherubism, an autosomal dominant autoinflammatory disorder associated with craniofacial dysmorphia. In this review, we summarize the diverse biological processes, including bone dynamics, metabolism, and Toll-like receptor (TLR) signaling controlled by tankyrase-mediated PARsylation of 3BP2, and highlight the therapeutic potential of this pathway.
摘要：
通过ADP-核糖(PARsylation)对蛋白质的修饰由聚(ADP-核糖)聚合酶(PARP)家族的酶催化,所述酶以PARP1为例,其控制染色质组织和DNA修复。此外,PARsylation诱导其底物的泛素化和蛋白酶体降解,因为PARsylation产生E3-泛素连接酶的识别位点。衔接蛋白SH3-结构域结合蛋白2（3BP2）的稳态水平受到端粒酶（PARP5）的负调控，它通过E3连接酶环指蛋白146（RNF146）协调3BP2的泛素化。3BP2错义突变使3BP2与tankyrase介导的负调控解偶联，并引起基会障碍，与颅面畸形相关的常染色体显性自身炎性疾病。在这次审查中,我们总结了不同的生物过程，包括骨骼动力学，新陈代谢，和Toll样受体（TLR）信号由tankyrase介导的3BP2PARsylation控制，并强调了该途径的治疗潜力。
