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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 B55δ subunit (PP2A:B55δ), 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:B55δ and its regulation by Greatwall kinase. Our model is consistent with what is already known about the regulation of CDK and PP2A:B55δ in frog eggs, and it suggests a previously undescribed role for the Greatwall-PP2A:B55δ interaction in creating a toggle switch for activation of the anaphase-promoting complex as embryonic cells exit mitosis and return to interphase.

Original publication

DOI

10.1073/pnas.1318065110

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

17/12/2013

Volume

110

Pages

20539 - 20544

Keywords

bistability, hysteresis, mitotic control, Anaphase-Promoting Complex-Cyclosome, Animals, Biological Clocks, Cell-Free System, Cyclin-Dependent Kinases, Embryo, Nonmammalian, Mitosis, Models, Biological, Oocytes, Protein Phosphatase 2, Protein-Serine-Threonine Kinases, Xenopus Proteins, Xenopus laevis