CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells

Dev Cell. 2002 Sep;3(3):339-50. doi: 10.1016/s1534-5807(02)00258-7.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Centrosome / physiology*
  • Cloning, Molecular
  • Cyclin-Dependent Kinases / physiology*
  • DNA, Complementary / analysis
  • G1 Phase
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • In Situ Hybridization, Fluorescence
  • Microtubule-Associated Proteins
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Phosphorylation
  • Polyploidy
  • RNA, Small Interfering / metabolism
  • Recombinant Proteins / metabolism
  • S Phase
  • Sensitivity and Specificity
  • Sequence Alignment
  • Substrate Specificity
  • Tumor Cells, Cultured


  • CCP110 protein, human
  • Cell Cycle Proteins
  • DNA, Complementary
  • Microtubule-Associated Proteins
  • Phosphoproteins
  • RNA, Small Interfering
  • Recombinant Proteins
  • Cyclin-Dependent Kinases