title: Bistability of mitotic entry and exit switches during open mitosis in mammalian cells.
abstract: Mitotic entry and exit are switch-like transitions that are driven by the activation and inactivation of Cdk1 and mitotic cyclins. This simple on/off reaction turns out to be a complex interplay of various reversible reactions, feedback loops, and thresholds that involve both the direct regulators of Cdk1 and its counteracting phosphatases. In this review, we summarize the interplay of the major components of the system and discuss how they work together to generate robustness, bistability, and irreversibility. We propose that it may be beneficial to regard the entry and exit reactions as two separate reversible switches that are distinguished by differences in the state of phosphatase activity, mitotic proteolysis, and a dramatic rearrangement of cellular components after nuclear envelope breakdown, and discuss how the major Cdk1 activity thresholds could be determined for these transitions.
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
authors.forename: Nadia
authors.initials: N
authors.lastname: Hégarat
authors.affiliation: Department of Biochemistry, Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UK.
authors.forename: Scott
authors.initials: S
authors.lastname: Rata
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
authors.forename: Helfrid
authors.initials: H
authors.lastname: Hochegger
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000502:physiology*; D006801:Humans; D008938:Mitosis
chemical_list: D018797:Cell Cycle Proteins
keywords: Cdc25; Greatwall; MPF; Wee1; mammalian cells; mitosis