Zhao Bing-Wang, Sun Si-Min, Xu Ke, Li Yuan-Yuan, Lei Wen-Long, Li Li, Liu Sai-Li, Ouyang Ying-Chun, Sun Qing-Yuan, Wang Zhen-Bo
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Cell Dev Biol. 2021 Mar 25;9:647103. doi: 10.3389/fcell.2021.647103. eCollection 2021.
There are two important events in oocyte meiotic maturation, the G2/M transition and metaphase I progression. Thousands of proteins participate in regulating oocyte maturation, which highlights the importance of the ubiquitin proteasome system (UPS) in regulating protein synthesis and degradation. Skp1-Cullin-F-box (SCF) complexes, as the best characterized ubiquitin E3 ligases in the UPS, specifically recognize their substrates. F-box proteins, as the variable adaptors of SCF, can bind substrates specifically. Little is known about the functions of the F-box proteins in oocyte maturation. In this study, we found that depletion of FBXO34, an F-box protein, led to failure of oocyte meiotic resumption due to a low activity of MPF, and this phenotype could be rescued by exogenous overexpression of CCNB1. Strikingly, overexpression of FBXO34 promoted germinal vesicle breakdown (GVBD), but caused continuous activation of spindle assembly checkpoint (SAC) and MI arrest of oocytes. Here, we demonstrated that FBXO34 regulated both the G2/M transition and anaphase entry in meiotic oocytes.
卵母细胞减数分裂成熟过程中有两个重要事件,即G2/M转换和减数第一次分裂中期进程。数千种蛋白质参与调节卵母细胞成熟,这凸显了泛素蛋白酶体系统(UPS)在调节蛋白质合成与降解方面的重要性。Skp1-Cullin-F-box(SCF)复合体作为UPS中特征最明确的泛素E3连接酶,能特异性识别其底物。F-box蛋白作为SCF的可变衔接子,可特异性结合底物。关于F-box蛋白在卵母细胞成熟中的功能知之甚少。在本研究中,我们发现F-box蛋白FBXO34的缺失导致卵母细胞减数分裂恢复失败,原因是MPF活性较低,而这种表型可通过外源性过表达CCNB1来挽救。令人惊讶的是,FBXO34的过表达促进了生发泡破裂(GVBD),但导致纺锤体组装检查点(SAC)持续激活以及卵母细胞减数第一次分裂中期阻滞。在此,我们证明了FBXO34调节减数分裂卵母细胞中的G2/M转换和后期进入。