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Vol. 17, Issue 8, 3423-3434, August 2006

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CP110 Cooperates with Two Calcium-binding Proteins to Regulate Cytokinesis and Genome Stability

William Y. Tsang^*, Alexander Spektor^*, Daniel J. Luciano^*, Vahan B. Indjeian, Zhihong Chen, Jeffery L. Salisbury, Irma Sánchez^*, and Brian David Dynlacht^*

*Department of Pathology, New York University School of Medicine, New York, NY 10016; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; Esai Research Institute, Andover, MA 01810; and Tumor Biology Program, Mayo Clinic, Rochester, MN 55905

Submitted May 1, 2006; Revised May 18, 2006; Accepted May 25, 2006
Monitoring Editor: Trisha Davis

The centrosome is an integral component of the eukaryotic cell cycle machinery, yet very few centrosomal proteins have been fully characterized to date. We have undertaken a series of biochemical and RNA interference (RNAi) studies to elucidate a role for CP110 in the centrosome cycle. Using a combination of yeast two-hybrid screens and biochemical analyses, we report that CP110 interacts with two different Ca²⁺-binding proteins, calmodulin (CaM) and centrin, in vivo. In vitro binding experiments reveal a direct, robust interaction between CP110 and CaM and the existence of multiple high-affinity CaM-binding domains in CP110. Native CP110 exists in large (300 kDa to 3 MDa) complexes that contain both centrin and CaM. We investigated a role for CP110 in CaM-mediated events using RNAi and show that its depletion leads to a failure at a late stage of cytokinesis and the formation of binucleate cells, mirroring the defects resulting from ablation of either CaM or centrin function. Importantly, expression of a CP110 mutant unable to bind CaM also promotes cytokinesis failure and binucleate cell formation. Taken together, our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis.

Address correspondence to: Brian David Dynlacht ( brian.dynlacht{at}med.nyu.edu)

Abbreviations used: CaM, calmodulin; CDK, cyclin-dependent kinase; RNAi, RNA interference; siRNA, small interfering RNA

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