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

Masaru Okuda; Henning F. Horn; Pheruza Tarapore; Yukari Tokuyama; A. George Smulian; Pui Kwong Chan; Erik S. Knudsen; Irene A. Hofmann; Jean D. Snyder; Kevin E. Bove; Kenji Fukasawa

doi:10.1016/S0092-8674(00)00093-3

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

Masaru Okuda, Henning F. Horn, Pheruza Tarapore, Yukari Tokuyama, A. George Smulian, Pui Kwong Chan, Erik S. Knudsen, Irene A. Hofmann, Jean D. Snyder, Kevin E. Bove, Kenji Fukasawa

Pathology

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576 Scopus citations

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.

Original language	English (US)
Pages (from-to)	127-140
Number of pages	14
Journal	Cell
Volume	103
Issue number	1
DOIs	https://doi.org/10.1016/S0092-8674(00)00093-3
State	Published - Sep 29 2000

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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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.",

author = "Masaru Okuda and Horn, {Henning F.} and Pheruza Tarapore and Yukari Tokuyama and Smulian, {A. George} and Chan, {Pui Kwong} and Knudsen, {Erik S.} and Hofmann, {Irene A.} and Snyder, {Jean D.} and Bove, {Kevin E.} and Kenji Fukasawa",

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T1 - Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication

AU - Okuda, Masaru

AU - Horn, Henning F.

AU - Tarapore, Pheruza

AU - Tokuyama, Yukari

AU - Smulian, A. George

AU - Chan, Pui Kwong

AU - Knudsen, Erik S.

AU - Hofmann, Irene A.

AU - Snyder, Jean D.

AU - Bove, Kevin E.

AU - Fukasawa, Kenji

PY - 2000/9/29

Y1 - 2000/9/29

N2 - 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.

AB - 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.

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EP - 140

JO - Cell

JF - Cell

IS - 1

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

Abstract

ASJC Scopus subject areas

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