title: Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication.
abstract: In animal cells, duplication of centrosomes and DNA is coordinated. Since CDK2/cyclin E triggers initiation of both events, activation of CDK2/cyclin E is thought to link these two events. We identified nucleophosmin (NPM/B23) as a substrate of CDK2/cyclin E in centrosome duplication. NPM/B23 associates specifically with unduplicated centrosomes, and NPM/B23 dissociates from centrosomes by CDK2/cyclin E-mediated phosphorylation. An anti-NPM/B23 antibody, which blocks this phosphorylation, suppresses the initiation of centrosome duplication in vivo. Moreover, expression of a nonphosphorylatable mutant NPM/ B23 in cells effectively blocks centrosome duplication. Thus, NPM/B23 is a target of CDK2/cyclin E in the initiation of centrosome duplication.
authors.affiliation: Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Ohio 45267, USA.
authors.forename: M
authors.initials: M
authors.lastname: Okuda
authors.forename: H F
authors.initials: HF
authors.lastname: Horn
authors.forename: P
authors.initials: P
authors.lastname: Tarapore
authors.forename: Y
authors.initials: Y
authors.lastname: Tokuyama
authors.forename: A G
authors.initials: AG
authors.lastname: Smulian
authors.forename: P K
authors.initials: PK
authors.lastname: Chan
authors.forename: E S
authors.initials: ES
authors.lastname: Knudsen
authors.forename: I A
authors.initials: IA
authors.lastname: Hofmann
authors.forename: J D
authors.initials: JD
authors.lastname: Snyder
authors.forename: K E
authors.initials: KE
authors.lastname: Bove
authors.forename: K
authors.initials: K
authors.lastname: Fukasawa
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D042846:CDC2-CDC28 Kinases; D018385:Centrosome / Q000378:metabolism*; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D008845:Microinjections; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics* / Q000302:isolation & purification; D000090243:Nucleophosmin; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000906:Antibodies; D019927:Cyclin E; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases