title: Nucleophosmin/B23 activates Aurora A at the centrosome through phosphorylation of serine 89.
abstract: Aurora A (AurA) is a major mitotic protein kinase involved in centrosome maturation and spindle assembly. Nucleophosmin/B23 (NPM) is a pleiotropic nucleolar protein involved in a variety of cellular processes including centrosome maturation. In the present study, we report that NPM is a strong activator of AurA kinase activity. NPM and AurA coimmunoprecipitate and colocalize to centrosomes in G2 phase, where AurA becomes active. In contrast with previously characterized AurA activators, NPM does not trigger autophosphorylation of AurA on threonine 288. NPM induces phosphorylation of AurA on serine 89, and this phosphorylation is necessary for activation of AurA. These data were confirmed in vivo, as depletion of NPM by ribonucleic acid interference eliminated phosphorylation of CDC25B on S353 at the centrosome, indicating a local loss of AurA activity. Our data demonstrate that NPM is a strong activator of AurA kinase activity at the centrosome and support a novel mechanism of activation for AurA.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche UMR6290, 35043 Rennes, France.
authors.forename: David
authors.initials: D
authors.lastname: Reboutier
authors.forename: Marie-Bérengère
authors.initials: MB
authors.lastname: Troadec
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cremet
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukasawa
authors.forename: Claude
authors.initials: C
authors.lastname: Prigent
mesh_terms: D064127:Aurora Kinases; D018385:Centrosome / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D012694:Serine; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases