Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication.
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.
Okuda
M
M
Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Ohio 45267, USA.
Horn
H F
HF
Tarapore
P
P
Tokuyama
Y
Y
Smulian
A G
AG
Chan
P K
PK
Knudsen
E S
ES
Hofmann
I A
IA
Snyder
J D
JD
Bove
K E
KE
Fukasawa
K
K
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
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