Entry into mitosis: a solution to the decades-long enigma of MPF.
Entry into mitosis: a solution to the decades-long enigma of MPF.
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DOI：
10.1007/s00412-015-0508-y
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发表时间：
2015-12
期刊：
影响因子：
1.6
通讯作者：
Kishimoto T
中科院分区：
文献类型：
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作者：
Kishimoto T
成熟或M期促进因子（MPF）是真核细胞普遍存在的M期诱导剂。MPF最初被定义为一种可转移的活性，可以在受体细胞中诱导G2/M相变。然而，今天，MPF被认为描述了一种在供体细胞中显示其作用的活性，而且，MPF始终与激酶周期蛋白B-Cdk1等同。然而，在某些情况下，即使细胞周期蛋白B-Cdk1完全活跃，MPF也无法检测到。三十多年来，这种不一致一直是一个长期存在的难题。MPF被定义为一种在受体细胞中表现出其作用的活性，它至少由两种独立的激酶组成，即细胞周期蛋白B-Cdk1和Greatwall (Gwl)，这一解释解开了这个谜团。Gwl参与MPF可以通过其对周期蛋白B-Cdk1的自调节激活的贡献和对周期蛋白B-Cdk1底物磷酸化的稳定来解释，这两者在MPF诱导受体细胞G2/M相变时都是必不可少的。为了完成这些任务，Gwl通过抑制抑制细胞周期蛋白B-Cdk1的蛋白磷酸酶2A (PP2A)-B55来帮助细胞周期蛋白B-Cdk1。MPF，正如最初定义的那样，因此不是周期蛋白B-Cdk1的同义词，而是一个由指导有丝分裂进入的周期蛋白B-Cdk1和抑制抗周期蛋白B-Cdk1磷酸酶的Gwl组成的系统。因此，目前认为MPF是供体细胞中周期蛋白B-Cdk1的同义词的观点是不精确的；相反，MPF被认为是参与细胞周期蛋白B-Cdk1自动调节激活的整个途径，具体取决于实验系统。
Maturation or M phase-promoting factor (MPF) is the universal inducer of M phase common to eukaryotic cells. MPF was originally defined as a transferable activity that can induce the G2/M phase transition in recipient cells. Today, however, MPF is assumed to describe an activity that exhibits its effect in donor cells, and furthermore, MPF is consistently equated with the kinase cyclin B-Cdk1. In some conditions, however, MPF, as originally defined, is undetectable even though cyclin B-Cdk1 is fully active. For over three decades, this inconsistency has remained a long-standing puzzle. The enigma is now resolved through the elucidation that MPF, defined as an activity that exhibits its effect in recipient cells, consists of at least two separate kinases, cyclin B-Cdk1 and Greatwall (Gwl). Involvement of Gwl in MPF can be explained by its contribution to the autoregulatory activation of cyclin B-Cdk1 and by its stabilization of phosphorylations on cyclin B-Cdk1 substrates, both of which are essential when MPF induces the G2/M phase transition in recipient cells. To accomplish these tasks, Gwl helps cyclin B-Cdk1 by suppressing protein phosphatase 2A (PP2A)-B55 that counteracts cyclin B-Cdk1. MPF, as originally defined, is thus not synonymous with cyclin B-Cdk1, but is instead a system consisting of both cyclin B-Cdk1 that directs mitotic entry and Gwl that suppresses the anti-cyclin B-Cdk1 phosphatase. The current view that MPF is a synonym for cyclin B-Cdk1 in donor cells is thus imprecise; instead, MPF is best regarded as the entire pathway involved in the autoregulatory activation of cyclin B-Cdk1, with specifics depending on the experimental system.