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Nat Com:浙大生研院范衡宇课题组发文阐述CRL4泛素连接酶在卵母细胞减数分裂中的作用

摘要 : 2015年8月18日在《Nature Communications》杂志发表浙江大学生命科学研究院范衡宇教授实验室研究论文,题目为“CRL4-DCAF1 Ubiquitin E3 Ligase Directs Protein Phosphatase 2A Degradation to Control Oocyte Meiotic Maturation”

 2015年8月18日在《Nature Communications》杂志发表浙江大学生命科学研究院范衡宇教授实验室研究论文,题目为“CRL4-DCAF1 Ubiquitin E3 Ligase Directs Protein Phosphatase 2A Degradation to Control Oocyte Meiotic Maturation”,其中范衡宇博士是本文通讯作者,博士研究生余超是本文第一作者,博士研究生嵇姝妍和硕士研究生沙倩倩并列本文第二作者。

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CRL4泛素连接酶对于体细胞的增殖、存活和基因组稳定性具有重要调节作用。但是,人们对于CRL4在哺乳动物卵母细胞中的作用还了解甚少,特别是CRL4在细胞分裂和染色体分离中的功能和机制还很不清楚。

继2013年范衡宇课题组在《Science》杂志发表研究论文、首次阐明了CRL4在防止卵巢早衰和延缓更年期中的作用以后,在本研究中进一步利用基因敲除小鼠为模型,研究了该蛋白复合体在卵母细胞成熟中的作用,实时观察了CRL4敲除以后卵母细胞减数分裂的进程,发现CRL4对于卵母细胞减数分裂细胞周期的顺利进行和同源染色体的正确分离至关重要。CRL4通过其底物识别蛋白DCAF1结合卵母细胞中的重要蛋白磷酸酶PP2A,使其泛素化并被降解,推动减数分裂的细胞周期进程,促进同源染色体分离和卵子的极体排放。该文章的创新性意义在于:1、首次研究了CRL4泛素连接酶在减数分裂细胞周期调控中的生理功能;2、首次发现了细胞中重要蛋白磷酸酶PP2A的泛素化降解机制;3、首次揭示减数分裂过程中PP2A的降解是卵子成熟和受精的重要前提条件。

原文链接:

CRL4–DCAF1 ubiquitin E3 ligase directs protein phosphatase 2A degradation to control oocyte meiotic maturation

原文摘要:

Oocyte meiosis is a specialized cell cycle that gives rise to fertilizable haploid gametes and is precisely controlled in various dimensions. We recently found that E3 ubiquitin ligase CRL4 is required for female fertility by regulating DNA hydroxymethylation to maintain oocyte survival and to promote zygotic genome reprogramming. However, not all phenotypes of CRL4-deleted oocytes could be explained by this mechanism. Here we show that CRL4 controls oocyte meiotic maturation by proteasomal degradation of protein phosphatase 2A scaffold subunit, PP2A-A. Oocyte-specific deletion of DDB1 or DCAF1 (also called VPRBP) results in delayed meiotic resumption and failure to complete meiosis I along with PP2A-A accumulation. DCAF1 directly binds to and results in the poly-ubiquitination of PP2A-A. Moreover, combined deletion of Ppp2r1a rescues the meiotic defects caused by DDB1/DCAF1 deficiency. These results provide in vivo evidence that CRL4-directed PP2A-A degradation is physiologically essential for regulating oocyte meiosis and female fertility.

来源: Nature Communications 浏览次数:0

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