Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
Int J Surg. 2024 Aug 1;110(8):4947-4964. doi: 10.1097/JS9.0000000000001541.
Ubiquitinases are known to catalyze ubiquitin chains on target proteins to regulate various physiological functions like cell proliferation, autophagy, apoptosis, and cell cycle progression. As a member of E3 ligase, ubiquitin protein ligase E3 component n-recognin 5 (UBR5) belongs to the HECT E3 ligase and has been reported to be correlated with various pathophysiological processes. In this review, the authors give a comprehensive insight into the structure and function of UBR5. The authors discuss the specific domains of UBR5 and explore their biological functions separately. Furthermore, the authors describe the involvement of UBR5 in different pathophysiological conditions, including immune response, virus infection, DNA damage response, and protein quality control. Moreover, the authors provide a thorough summary of the important roles and regulatory mechanisms of UBR5 in cancers and other diseases. On the whole, investigating the domains and functions of UBR5, elucidating the underlying mechanisms of UBR5 with various substrates in detail may provide new theoretical basis for the treatment of diseases, including cancers, which could improve future studies to construct novel UBR5-targeted therapy strategies.
泛素酶已知能够在靶蛋白上催化泛素链，以调节各种生理功能，如细胞增殖、自噬、细胞凋亡和细胞周期进程。作为 E3 连接酶的一员，泛素蛋白连接酶 E3 成分 n-识别蛋白 5（UBR5）属于 HECT E3 连接酶，已被报道与各种病理生理过程相关。在这篇综述中，作者全面深入地了解了 UBR5 的结构和功能。作者讨论了 UBR5 的特定结构域，并分别探讨了它们的生物学功能。此外，作者还描述了 UBR5 在不同病理生理条件下的参与情况，包括免疫反应、病毒感染、DNA 损伤反应和蛋白质质量控制。此外，作者还全面总结了 UBR5 在癌症和其他疾病中的重要作用和调节机制。总的来说，研究 UBR5 的结构域和功能，详细阐明 UBR5 与各种底物的潜在机制，可能为包括癌症在内的疾病的治疗提供新的理论基础，这可以改进未来的研究，构建新型 UBR5 靶向治疗策略。
