Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication.
basic_science · Level V
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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.
Medical subject headings
- CDC2-CDC28 Kinases
- Centrosome
- Cyclin E
- Cyclin-Dependent Kinases
- Nuclear Proteins
- Protein Serine-Threonine Kinases