Abstract
Centrosome duplication and separation are linked inextricably to certain cell cycle events, in particular activation of cyclin-dependent kinases (CDKs). However, relatively few CDK targets driving these events have been uncovered. Here, we have performed a screen for CDK substrates and have isolated a target, CP110, which is phosphorylated by CDKs in vitro and in vivo. Human CP110 localizes to centrosomes. Its expression is strongly induced at the G1-to-S phase transition, coincident with the initiation of centrosome duplication. RNAi-mediated depletion of CP110 indicates that this protein plays an essential role in centrosome duplication. Long-term disruption of CP110 phosphorylation leads to unscheduled centrosome separation and overt polyploidy. Our data suggest that CP110 is a physiological centrosomal CDK target that promotes centrosome duplication, and its deregulation may contribute to genomic instability.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / physiology*
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Centrosome / physiology*
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Cloning, Molecular
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Cyclin-Dependent Kinases / physiology*
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DNA, Complementary / analysis
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G1 Phase
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Gene Expression Regulation
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HeLa Cells
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Humans
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In Situ Hybridization, Fluorescence
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Microtubule-Associated Proteins
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Phosphoproteins / genetics
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Phosphoproteins / physiology*
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Phosphorylation
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Polyploidy
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RNA, Small Interfering / metabolism
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Recombinant Proteins / metabolism
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S Phase
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Sensitivity and Specificity
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Sequence Alignment
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Substrate Specificity
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Tumor Cells, Cultured
Substances
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CCP110 protein, human
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Cell Cycle Proteins
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DNA, Complementary
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Microtubule-Associated Proteins
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Phosphoproteins
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RNA, Small Interfering
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Recombinant Proteins
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Cyclin-Dependent Kinases