title: 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 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.
authors.affiliation: Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom.
authors.forename: Tongli
authors.initials: T
authors.lastname: Zhang
authors.forename: John J
authors.initials: JJ
authors.lastname: Tyson
authors.forename: Béla
authors.initials: B
authors.lastname: Novák
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001683:Biological Clocks; D002474:Cell-Free System / Q000201:enzymology; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D008938:Mitosis; D008954:Models, Biological; D009865:Oocytes / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D054648:Protein Phosphatase 2 / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D029867:Xenopus Proteins; D064173:Anaphase-Promoting Complex-Cyclosome; C544010:MASTL protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D054648:Protein Phosphatase 2
keywords: bistability; hysteresis; mitotic control