Role for regulated phosphatase activity in generating mitotic oscillations in Xenopus cell-free extracts

Abstract

Although current textbook explanations of cell-cycle control in eukaryotes emphasize the periodic activation of cyclin-dependent protein kinases (CDKs), recent experimental observations suggest a significant role for the periodic activation and inactivation of a CDK-counteracting protein phosphatase 2A with a B55λ subunit (PP2A:B55λ), during mitotic cycles in frog-egg extracts and early embryos. In this paper, we extend an earlier mathematical model of embryonic cell cycles to include experimentally motivated roles for PP2A:B55λ and its regulation by Greatwall kinase. Our model is consistent with what is already known about the regulation of CDK and PP2A:B55λ in frog eggs, and it suggests a previously undescribed role for the Greatwall- PP2A:B55λ interaction in creating a toggle switch for activation of the anaphase-promoting complex as embryonic cells exit mitosis and return to interphase.