title: Characterization of centrosomal association of nucleophosmin/B23 linked to Crm1 activity.
abstract: Nucleophosmin (NPM)/B23 is a multifunctional protein, involving in a wide variety of basic cellular processes, including ribosome assembly, DNA duplication, nucleocytoplasmic trafficking, and centrosome duplication. It has previously been shown that NPM/B23 localizes to centrosomes, and dissociate from centrosomes upon phosphorylation by Cdk2/cyclin E. However, detail characterization of centrosomal association of NPM/B23 has been hampered by the lack of appropriate antibodies that efficiently detects centrosomally localized NPM/B23, as well as by apparent loss of natural behavior of NPM/B23 when tagged with fluorescent proteins. Here, by the use of newly generated anti-NPM/B23 antibody, we conducted a careful analysis of centrosomal localization of NPM/B23. We found that NPM/B23 localizes between the paired centrioles of unduplicated centrosomes, suggesting the role of NPM/B23 in the centriole pairing. Upon initiation of centrosome duplication, some NPM/B23 proteins remain at mother centrioles of the parental centriole pairs. We further found that inhibition of Crm1 nuclear export receptor results in both accumulation of cyclin E at centrosomes and efficient dissociation of NPM/B23 from centrosomes.
authors.affiliation: Department of Cell Biology, University of Cincinnati College of Medicine, P.O. Box 670521 (3125 Eden Avenue), Cincinnati, OH 45267-0521, United States.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinmura
authors.forename: Pheruza
authors.initials: P
authors.lastname: Tarapore
authors.forename: Yukari
authors.initials: Y
authors.lastname: Tokuyama
authors.forename: Kyle R
authors.initials: KR
authors.lastname: George
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukasawa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002453:Cell Cycle; D002502:Centrioles / Q000378:metabolism; D018385:Centrosome; D019927:Cyclin E / Q000378:metabolism; D018604:Epitope Mapping; D007150:Immunohistochemistry; D028884:Karyopherins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D000090243:Nucleophosmin; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D000097606:Exportin 1 Protein
chemical_list: D000911:Antibodies, Monoclonal; D019927:Cyclin E; D028884:Karyopherins; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C000715570:Npm1 protein, mouse