CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells.
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.
Pubmed ID: 12361598 RIS Download
Amino Acid Motifs | Amino Acid Sequence | Cell Cycle Proteins | Centrosome | Cloning, Molecular | Cyclin-Dependent Kinases | DNA, Complementary | G1 Phase | Gene Expression Regulation | HeLa Cells | Humans | In Situ Hybridization, Fluorescence | Microtubule-Associated Proteins | Molecular Sequence Data | Mutagenesis, Site-Directed | Phosphoproteins | Phosphorylation | Polyploidy | RNA, Small Interfering | Recombinant Proteins | S Phase | Sensitivity and Specificity | Sequence Alignment | Substrate Specificity | Tumor Cells, Cultured