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PMID: 11051553 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication.

Cell ·Vol. 103 ·No. 1 ·2000-09-29 ·Pages 127-40

Okuda M, Horn HF, Tarapore P, Tokuyama Y, Smulian AG, Chan PK, Knudsen ES, Hofmann IA, Snyder JD, Bove KE, Fukasawa K

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.

MeSH Terms
3T3 Cells Animals Antibodies/pharmacology CDC2-CDC28 Kinases Centrosome/metabolism Cyclin E/genetics,metabolism Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases/genetics,metabolism Gene Deletion Gene Expression Regulation/physiology Mice Microinjections Mutation/genetics Nuclear Proteins/deficiency,genetics,isolation & purification Nucleophosmin Phosphorylation Protein Serine-Threonine Kinases/genetics,metabolism
Chemicals
Antibodies Cyclin E Npm1 protein, mouse Nuclear Proteins Nucleophosmin Protein Serine-Threonine Kinases CDC2-CDC28 Kinases Cdk2 protein, mouse Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Okuda M
Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Ohio 45267, USA.
Horn H F
Tarapore P
Tokuyama Y
Smulian A G
Chan P K
Knudsen E S
Hofmann I A
Snyder J D
Bove K E
Fukasawa K
Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
Published
2000-09-29
Pages
127-40
Language
English
Region
United States
NLM ID
0413066
Subset
IM
Grants
NCI NIH HHS · R01 CA090522-01 · United States
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