title: A role for Ral GTPase-activating protein subunit β in mitotic regulation.
abstract: Ral proteins are small GTPases that play critical roles in normal physiology and in oncogenesis. There is little information on the GTPase-activating proteins (GAPs) that downregulate their activity. Here, we provide evidence that the noncatalytic β subunit of RalGAPα1/2 β complexes is involved in mitotic control. RalGAPβ localizes to the Golgi and nucleus during interphase, and relocalizes to the mitotic spindle and cytokinetic intercellular bridge during mitosis. Depletion of RalGAPβ causes chromosome misalignment and decreases the amount of mitotic cyclin B1, disturbing the metaphase-to-anaphase transition. Overexpression of RalGAPβ interferes with cell division, leading to binucleation and multinucleation, and cell death. We propose that RalGAPβ plays an essential role in the sequential progression of mitosis by controlling the spatial and temporal activation of Ral GTPases in the spindle assembly checkpoint (SAC) and cytokinesis. Deregulation of RalGAPβ might cause genomic instability, leading to human carcinogenesis.
authors.affiliation: Institut Pasteur, Unité des interactions Bactéries cellules, Paris, France; Inserm, U604, Paris, France; INRA, USC2020, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Personnic
authors.forename: Goran
authors.initials: G
authors.lastname: Lakisic
authors.forename: Edith
authors.initials: E
authors.lastname: Gouin
authors.forename: Alix
authors.initials: A
authors.lastname: Rousseau
authors.forename: Alexis
authors.initials: A
authors.lastname: Gautreau
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
authors.forename: Hélène
authors.initials: H
authors.lastname: Bierne
mesh_terms: D000705:Anaphase; D016923:Cell Death; D045744:Cell Line, Tumor; D002846:Chromatography, Affinity; D020090:Chromosome Segregation; D020690:GTPase-Activating Proteins / Q000378:metabolism / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008677:Metaphase; D008938:Mitosis; D009419:Nerve Tissue Proteins / Q000378:metabolism; D021381:Protein Transport; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D020725:ral GTP-Binding Proteins / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; C495326:RALGAPA1 protein, human; C514562:RALGAPA2 protein, human; C000591277:RALGAPB protein, human; D014404:Tubulin; C492198:RALA protein, human; D020725:ral GTP-Binding Proteins
keywords: RalA; RalB; RalGAP; mitosis; spindle