Entry into mitosis: a solution to the decades-long enigma of MPF

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.