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.
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D018385:Centrosome / Q000502:physiology*; D003001:Cloning, Molecular; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D018076:DNA, Complementary / Q000032:analysis; D016193:G1 Phase; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D011123:Polyploidy; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D016196:S Phase; D012680:Sensitivity and Specificity; D016415:Sequence Alignment; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
C467559:CCP110 protein, human; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D018844:Cyclin-Dependent Kinases