title: Activation of cyclin B1-Cdk1 synchronizes events in the nucleus and the cytoplasm at mitosis.
abstract: The cyclin B-Cdk1 kinase triggers mitosis in most eukaryotes. In animal cells, cyclin B shuttles between the nucleus and cytoplasm in interphase before rapidly accumulating in the nucleus at prophase, which promotes disassembly of the nuclear lamina and nuclear envelope breakdown (NEBD). What triggers the nuclear accumulation of cyclin B1 is presently unclear, although the prevailing view is that the Plk1 kinase inhibits its nuclear export. In this study, we use a biosensor specific for cyclin B1-Cdk1 activity to show that activating cyclin B1-Cdk1 immediately triggers its rapid accumulation in the nucleus through a 40-fold increase in nuclear import that remains dependent on Cdk1 activity until NEBD. Nevertheless, a substantial proportion of cyclin B1-Cdk1 remains in the cytoplasm. The increase in nuclear import is driven by changes in the nuclear import machinery that require neither Plk1 nor inhibition of nuclear export. Thus, the intrinsic link between cyclin B1-Cdk1 activation and its rapid nuclear import inherently coordinates the reorganization of the nucleus and the cytoplasm at mitotic entry.
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, England, UK. olivier.gavet@gurdon.cam.ac.uk
authors.forename: Olivier
authors.initials: O
authors.lastname: Gavet
authors.forename: Jonathon
authors.initials: J
authors.lastname: Pines
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D015374:Biosensing Techniques; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020666:ras-GRF1 / Q000235:genetics / Q000378:metabolism
chemical_list: D056744:Cyclin B1; D004791:Enzyme Inhibitors; D011993:Recombinant Fusion Proteins; D020666:ras-GRF1; D016203:CDC2 Protein Kinase
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