The SUMO Protease SENP3 Orchestrates G2-M Transition and Spindle Assembly in Mouse Oocytes.
The SUMO Protease SENP3 Orchestrates G2-M Transition and Spindle Assembly in Mouse Oocytes.
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SUMO 蛋白酶 SENP3 协调小鼠卵母细胞中的 G2-M 转变和纺锤体组装
DOI：
10.1038/srep15600
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发表时间：
2015-10-23
影响因子：
4.6
通讯作者：
Huo LJ
中科院分区：
文献类型：
--
作者：
Huang CJ;Wu D;Khan FA;Huo LJ
卵母细胞减数分裂是一个转录静止过程，细胞周期进程由多种翻译后修饰协调，包括SUMOylation。SENP3是一种重要的去硫酰基化蛋白酶，在核糖体生物发生和氧化应激中得到了广泛的研究。然而，SENP3在细胞周期调控中的作用仍然是谜，特别是在卵母细胞减数分裂成熟中。本研究发现，在卵母细胞减数分裂过程中，SENP3与纺锤体共定位，SENP3的沉默严重影响了M期进入（生发囊泡破裂，GVBD）和第一极体挤压（PBI）。极体挤压失败的原因是γ-微管蛋白功能紊乱，导致纺锤体形态发生缺陷。SENP3缺失导致定位错误和Aurora a （MTOCs定位和纺锤体动力学的必需蛋白）大量丢失，而Bora （Aurora a的结合伴侣和激活剂）在细胞质中不规则分散分布，而不是集中在纺锤体上。SENP3 RNAi使SUMO-2/3而非SUMO-1偶联物整体减少。此外，纺锤体组装检查点在SENP3 RNAi上保持功能。我们的研究结果通过探索SENP3在小鼠卵母细胞减数分裂成熟过程中在减数分裂恢复、纺锤体组装和极体发射中的作用，更新了SENP3的功能，这可能是由于其促进SUMO-2/3成熟的蛋白水解活性。
Oocyte meiosis is a transcription quiescence process and the cell-cycle progression is coordinated by multiple post-translational modifications, including SUMOylation. SENP3 an important deSUMOylation protease has been intensively studied in ribosome biogenesis and oxidative stress. However, the roles of SENP3 in cell-cycle regulation remain enigmatic, particularly for oocyte meiotic maturation. Here, we found that SENP3 co-localized with spindles during oocyte meiosis and silencing of SENP3 severely compromised the M phase entry (germinal vesicle breakdown, GVBD) and first polar body extrusion (PBI). The failure in polar body extrusion was due to the dysfunction of γ-tubulin that caused defective spindle morphogenesis. SENP3 depletion led to mislocalization and a substantial loss of Aurora A (an essential protein for MTOCs localization and spindle dynamics) while irregularly dispersed distribution of Bora (a binding partner and activator of Aurora A) in cytoplasm instead of concentrating at spindles. The SUMO-2/3 but not SUMO-1 conjugates were globally decreased by SENP3 RNAi. Additionally, the spindle assembly checkpoint remained functional upon SENP3 RNAi. Our findings renew the picture of SENP3 function by exploring its role in meiosis resumption, spindle assembly and following polar body emission during mouse oocyte meiotic maturation, which is potentially due to its proteolytic activity that facilitate SUMO-2/3 maturation.