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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Antibodies / pharmacology
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CDC2-CDC28 Kinases*
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Centrosome / metabolism*
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Cyclin E / genetics*
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Cyclin E / metabolism
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases / genetics*
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Cyclin-Dependent Kinases / metabolism
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Gene Deletion
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Gene Expression Regulation / physiology
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Mice
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Microinjections
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Mutation / genetics
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Nuclear Proteins / deficiency
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Nuclear Proteins / genetics*
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Nuclear Proteins / isolation & purification
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Nucleophosmin
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Phosphorylation
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism
Substances
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Antibodies
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Cyclin E
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Npm1 protein, mouse
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Nuclear Proteins
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Nucleophosmin
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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Cdk2 protein, mouse
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases