Mastl is required for timely activation of APC/C in meiosis I and Cdk1 reactivation in meiosis II

被引:32
作者
Adhikari, Deepak [1 ]
Diril, M. Kasim [2 ]
Busayavalasa, Kiran [1 ]
Risal, Sanjiv [1 ]
Nakagawa, Shoma [3 ]
Lindkvist, Rebecca [1 ]
Shen, Yan [1 ]
Coppola, Vincenzo [4 ]
Tessarollo, Lino [4 ]
Kudo, Nobuaki R. [3 ]
Kaldis, Philipp [2 ,5 ]
Liu, Kui [1 ]
机构
[1] Univ Gothenburg, Dept Chem & Mol Biol, S-40530 Gothenburg, Sweden
[2] ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore
[3] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Inst Reprod & Dev Biol, Dept Surg & Canc, London W12 0NN, England
[4] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA
[5] Natl Univ Singapore, Dept Biochem, Singapore 117599, Singapore
基金
英国医学研究理事会; 瑞典研究理事会;
关键词
PROTEIN PHOSPHATASE 2A; CELL-CYCLE REGULATION; GREATWALL KINASE; MEIOTIC MATURATION; PHOSPHORYLATION; MITOSIS; PROGRESSION; CHECKPOINT; OOCYTES; ARPP19;
D O I
10.1083/jcb.201406033
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In mitosis, the Greatwall kinase (called microtubule-associated serine/threonine kinase like [Mastl] in mammals) is essential for prometaphase entry or progression by suppressing protein phosphatase 2A (PP2A) activity. PP2A suppression in turn leads to high levels of Cdk1 substrate phosphorylation. We have used a mouse model with an oocyte-specific deletion of Mastl to show that Mastl-null oocytes resume meiosis I and reach metaphase I normally but that the onset and completion of anaphase I are delayed. Moreover, after the completion of meiosis I, Mastl-null oocytes failed to enter meiosis II (MII) because they reassembled a nuclear structure containing decondensed chromatin. Our results show that Mastl is required for the timely activation of anaphase-promoting complex/cyclosome to allow meiosis I exit and for the rapid rise of Cdk1 activity that is needed for the entry into MII in mouse oocytes.
引用
收藏
页码:843 / 853
页数:11
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