title: Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression.
abstract: Cell division requires the coordination of critical protein kinases and phosphatases. Greatwall (Gwl) kinase activity inactivates PP2A-B55 at mitotic entry to promote the phosphorylation of cyclin B-Cdk1 substrates, but how Gwl is regulated is poorly understood. We found that the subcellular localization of Gwl changed dramatically during the cell cycle in Drosophila. Gwl translocated from the nucleus to the cytoplasm in prophase. We identified two critical nuclear localization signals in the central, poorly characterized region of Gwl, which are required for its function. The Polo kinase associated with and phosphorylated Gwl in this region, promoting its binding to 14-3-3ε and its localization to the cytoplasm in prophase. Our results suggest that cyclin B-Cdk1 phosphorylation of Gwl is also required for its nuclear exclusion by a distinct mechanism. We show that the nucleo-cytoplasmic regulation of Gwl is essential for its functions in vivo and propose that the spatial regulation of Gwl at mitotic entry contributes to the mitotic switch.
authors.affiliation: Institut de recherche en immunologie et en cancérologie, Université de Montréal, Montréal, Québec H3C 3J7, Canada.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Galan
authors.forename: Karine
authors.initials: K
authors.lastname: Normandin
authors.forename: Éric
authors.initials: É
authors.lastname: Bonneil
authors.forename: Gilles R
authors.initials: GR
authors.lastname: Hickson
authors.forename: Philippe P
authors.initials: PP
authors.lastname: Roux
authors.forename: Pierre
authors.initials: P
authors.lastname: Thibault
authors.forename: Vincent
authors.initials: V
authors.lastname: Archambault
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D002467:Cell Nucleus / Q000201:enzymology*; D002478:Cells, Cultured; D059006:Chromosomes, Insect / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D008297:Male; D008938:Mitosis; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D059008:Time-Lapse Imaging
chemical_list: D029721:Drosophila Proteins; C072004:polo protein, Drosophila; C490167:Gwl protein, Drosophila; D017346:Protein Serine-Threonine Kinases