Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APC(Cdh1).

Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APC(Cdh1).
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DOI:
10.1083/jcb.200607070
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发表时间:
2007-01-01
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Carroll J
Carroll J
中科院分区:
其他
文献类型:
--
作者:
Marangos P;Verschuren EW;Chen R;Jackson PK;Carroll J

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哺乳动物卵母细胞处于第一次减数分裂的前期。进入第一次减数分裂是由成熟促进因子(MPF)活性的增加所驱动的。在小鼠卵母细胞中,我们发现早期有丝分裂抑制剂1 (Emi1),一种后期促进复合物(APC)的抑制剂,负责细胞周期蛋白B的破坏和MPF的失活,存在于I前期,并在生发囊泡破坏(GVBD)后立即经历Skp1-Cul1-F-box /β trcp介导的破坏。外源性Emi1或抑制前驱卵母细胞中Emi1的破坏导致细胞周期蛋白B1-GFP的稳定,足以触发GVBD。相反,使用morpholino寡核苷酸消耗Emi1会增加细胞周期蛋白B1-GFP的破坏,导致MPF激活的衰减和进入第一次减数分裂的延迟。最后,我们发现emi1对减数分裂I的依赖性作用需要Cdh1的存在。这些观察结果揭示了一种控制进入第一次减数分裂的新机制:emi1依赖性抑制APCCdh1。
Mammalian oocytes are arrested in prophase of the first meiotic division. Progression into the first meiotic division is driven by an increase in the activity of maturation-promoting factor (MPF). In mouse oocytes, we find that early mitotic inhibitor 1 (Emi1), an inhibitor of the anaphase-promoting complex (APC) that is responsible for cyclin B destruction and inactivation of MPF, is present at prophase I and undergoes Skp1–Cul1–F-box/βTrCP-mediated destruction immediately after germinal vesicle breakdown (GVBD). Exogenous Emi1 or the inhibition of Emi1 destruction in prophase-arrested oocytes leads to a stabilization of cyclin B1–GFP that is sufficient to trigger GVBD. In contrast, the depletion of Emi1 using morpholino oligonucleotides increases cyclin B1–GFP destruction, resulting in an attenuation of MPF activation and a delay of entry into the first meiotic division. Finally, we show that Emi1-dependent effects on meiosis I require the presence of Cdh1. These observations reveal a novel mechanism for the control of entry into the first meiotic division: an Emi1-dependent inhibition of APCCdh1.
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