Zhang Xiaoying, Liu Yu'e, Zhang Tong, Tan Yuying, Dai Xiangpeng, Yang Yong-Guang, Zhang Xiaoling
Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital, Jilin University, Changchun, China.
National-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital, Jilin University, Changchun, China.
Front Immunol. 2023 Mar 17;14:1125224. doi: 10.3389/fimmu.2023.1125224. eCollection 2023.
Cullin-RING ligases (CRLs) are the largest class of E3 ubiquitin ligases regulating the stability and subsequent activity of a large number of important proteins responsible for the development and progression of various diseases, including autoimmune diseases (AIDs). However, the detailed mechanisms of the pathogenesis of AIDs are complicated and involve multiple signaling pathways. An in-depth understanding of the underlying regulatory mechanisms of the initiation and progression of AIDs will aid in the development of effective therapeutic strategies. CRLs play critical roles in regulating AIDs, partially by affecting the key inflammation-associated pathways such as NF-κB, JAK/STAT, and TGF-β. In this review, we summarize and discuss the potential roles of CRLs in the inflammatory signaling pathways and pathogenesis of AIDs. Furthermore, advances in the development of novel therapeutic strategies for AIDs through targeting CRLs are also highlighted.
Cullin-RING连接酶(CRLs)是最大一类E3泛素连接酶,可调节众多对包括自身免疫性疾病(AIDs)在内的各种疾病的发生和发展至关重要的蛋白质的稳定性及后续活性。然而,AIDs发病机制的详细过程很复杂,涉及多个信号通路。深入了解AIDs起始和进展的潜在调控机制将有助于开发有效的治疗策略。CRLs在调节AIDs中发挥关键作用,部分是通过影响关键的炎症相关通路,如NF-κB、JAK/STAT和TGF-β。在本综述中,我们总结并讨论了CRLs在AIDs炎症信号通路和发病机制中的潜在作用。此外,还重点介绍了通过靶向CRLs开发AIDs新型治疗策略的进展。