Lv Yi, Xing Feiyue
Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, China.
Turk J Biol. 2022 Feb 24;46(2):186-194. doi: 10.3906/biy-2106-63. eCollection 2022.
UBE2O as an atypical ubiquitin-conjugating enzyme possesses an E2-E3 hybrid enzyme activity. It can regulate substrate levels or transcriptional activities by cooperating with other E3 ubiquitin ligases or forming homomeric complexes displaying intrinsic E2 and E3 activities. UBE2O controls the quality of cell proteome including protein degradation, modification, transport and location. Recent studies reveal that UBE2O plays a vital role in intracellular protein ubiquitination processes by regulating BMP/SMAD, TRAF/NF-κB, mTOR/HIF1a and IL-1β/IRAK4 signaling pathways, c-Maf stability and BAP1 subcellular location, which is proposed as a quality control supervisor of multiprotein complexes for degradation. Its abnormality leads to a variety of physical activity disorders and even occurrence of cancer. UBE2O is entirely distinct in molecular structure and functions from other E2 ubiquitin ligase. Exploring and elucidating regulatory mechanism of UBE2O may identify novel crucial molecular targets so as to pave therapeutic approaches for ubiquitination-associated metabolic disorders and diseases. Here, we particularly feature regulatory pathways of UBE2O in orphans of multiprotein complexes for degradation and its potential application.
UBE2O作为一种非典型泛素结合酶，具有E2-E3杂合酶活性。它可以通过与其他E3泛素连接酶合作或形成具有内在E2和E3活性的同聚复合物来调节底物水平或转录活性。UBE2O控制细胞蛋白质组的质量，包括蛋白质降解、修饰、运输和定位。最近的研究表明，UBE2O通过调节BMP/SMAD、TRAF/NF-κB、mTOR/HIF1a和IL-1β/IRAK4信号通路、c-Maf稳定性和BAP1亚细胞定位，在细胞内蛋白质泛素化过程中发挥重要作用，这被认为是多蛋白复合物降解的质量控制监督者。其异常会导致多种身体活动障碍甚至癌症的发生。UBE2O在分子结构和功能上与其他E2泛素连接酶完全不同。探索和阐明UBE2O的调控机制可能会识别出新的关键分子靶点，从而为泛素化相关的代谢紊乱和疾病开辟治疗途径。在此，我们特别介绍UBE2O在多蛋白复合物降解中的调控途径及其潜在应用。
