Appropriate expression of Ube2C and Ube2S controls the progression of the first meiotic division
Appropriate expression of Ube2C and Ube2S controls the progression of the first meiotic division
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DOI：
10.1096/fj.15-274522
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发表时间：
2015-11-01
期刊：
影响因子：
4.8
通讯作者：
Dekel, Nava
中科院分区：
文献类型：
--
作者：
Ben-Eliezer, Inbal;Pomerantz, Yael;Dekel, Nava
细胞周期的蛋白质调节剂的及时降解对于完成细胞分裂是必不可少的。这种降解由E3后期促进复合物/环体（APC/C）促进，并由E2泛素缀合酶（Ube 2s）介导。与收集的关于减数分裂E3 APC/C的大量信息不同，参与这种细胞分裂的E2从未被研究过。我们确定Ube 2C，-S和-D3作为E2酶，调节小鼠卵母细胞减数分裂过程中的APC/C活性。它们的消耗减少了50%的第一次减数分裂胞质分裂的水平，和它们的过度表达加倍，并加速其完成（50%相比，4%在11小时）。我们还证明了这些E2参与确保适当的纺锤体形成。值得注意的是，高水平的Ube 2C导致第一次减数分裂的恢复，而不管纺锤体的形成，覆盖纺锤体组装检查点。因此，除了它们在蛋白质降解中的典型功能之外，Ube 2C和-S还控制第一极体的挤出。总的来说，我们的研究特点的新监管机构，并揭示了他们在减数分裂过程中发挥的新作用。这些发现揭示了卵母细胞染色体分离的可靠性，并可能有助于更好地了解非整倍体及其导致的遗传畸形。
Timely degradation of protein regulators of the cell cycle is essential for the completion of cell division. This degradation is promoted by the E3 anaphase-promoting complex/cyclosome(APC/C) and mediated by the E2 ubiquitin-conjugating enzymes (Ube2s). Unlike the ample information gathered regarding the meiotic E3 APC/C, the E2s participating in this cell division have never been studied. We identified Ube2C, -S, and -D3 as the E2 enzymes that regulate APC/C activity during meiosis of mouse oocytes. Their depletion reduces the levels of the first meiotic cytokinesis by 50%, and their overexpression doubles and accelerates its completion (50% as compared with 4% at 11 h). We also demonstrated that these E2s take part in ensuring appropriate spindle formation. It is noteworthy that high levels of Ube2C bring about the resumption of the first meiotic division, regardless of the formation of the spindle, overriding the spindle assembly checkpoint. Thus, alongside their canonical function in protein degradation, Ube2C and -S also control the extrusion of the first polar body. Overall, our study characterizes new regulators and unveils the novel roles they play during the meiotic division. These findings shed light on faithful chromosome segregation in oocytes and may contribute to better understanding of aneuploidy and its consequent genetic malformations.