Kazan Federal University, Kazan, Russian Federation.
Kazan Federal University, Kazan, Russian Federation.
Immunol Lett. 2018 Oct;202:44-51. doi: 10.1016/j.imlet.2018.08.001. Epub 2018 Aug 9.
Ubiquitin-proteasome system (UPS) is a primary signaling pathway for regulation of protein turnover and removal of misfolded proteins in eukaryotic cells. Enzymes of the UPS pathway - E1 activating, E2 conjugating, E3 ligating - act together to covalently tag substrate proteins with a chain of ubiquitins, small regulatory proteins. The poly-ubiquitin chain then serves as a recognition motif for 26S proteasome to recognize and degrade the substrate. In recent years UPS has emerged as attractive enzymatic cascade for development of novel therapeutics against various human diseases. Building on the previous success of targeting this pathway in cancer - the broader scientific community is currently looking for ways to elucidate functions of E3 ligases, substrate-specific members of the UPS. RING-type E3 ubiquitin ligases, the largest class of E3s, represent prospective targets for small molecule modulation and their importance is reinforced by ever growing evidence of playing role in non-cancer diseases, primarily associated with inflammatory and immune disorders. In this review, we aim to briefly cover the current knowledge of biological functions of RING-type E3 ligases in inflammation and immunity.
泛素-蛋白酶体系统（UPS）是真核细胞中调节蛋白质周转和清除错误折叠蛋白质的主要信号通路。UPS 途径的酶 - E1 激活酶、E2 连接酶、E3 连接酶 - 共同作用，将底物蛋白共价标记上一连串的泛素，这是一种小的调节蛋白。然后，多聚泛素链作为 26S 蛋白酶体的识别基序，以识别和降解底物。近年来，UPS 作为一种有吸引力的酶级联反应，已被用于开发针对各种人类疾病的新型治疗方法。在该途径在癌症治疗方面取得的先前成功的基础上，更广泛的科学界目前正在寻找阐明 E3 连接酶（UPS 的底物特异性成员）功能的方法。RING 型 E3 泛素连接酶是 E3 中最大的一类，代表了小分子调节的潜在靶点，而且它们在非癌症疾病中的作用越来越明显，主要与炎症和免疫紊乱有关，这进一步证实了它们的重要性。在这篇综述中，我们旨在简要介绍 RING 型 E3 连接酶在炎症和免疫中的生物学功能的现有知识。
