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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 51; pp. 20539 - 20544
• Main Authors: Zhang, Tongli, Tyson, John J., Novák, Béla
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.12.2013; NATIONAL ACADEMY OF SCIENCES; National Acad Sciences
• Subjects: Anaphase-Promoting Complex-Cyclosome - chemistry; Anaphase-Promoting Complex-Cyclosome - metabolism; Animals; Anura; Biological Clocks; Biological Sciences; Cell cycle; Cell-Free System - enzymology; Control loops; Cyclin-Dependent Kinases - chemistry; Cyclin-Dependent Kinases - metabolism; Cyclins; Eggs; Embryo, Nonmammalian - chemistry; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - enzymology; Embryonic cells; Eukaryotes; Frogs; Gene expression regulation; Interphase; Kinases; Mathematical models; Mitosis; Models, Biological; Oocytes - chemistry; Oocytes - cytology; Oocytes - enzymology; Phosphatases; Phosphorylation; Protein Phosphatase 2 - chemistry; Protein Phosphatase 2 - metabolism; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - metabolism; Xenopus; Xenopus laevis; Xenopus Proteins - chemistry; Xenopus Proteins - metabolism; bistability; mitotic control; hysteresis
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1318065110

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.