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β-Catenin is a Nek2 substrate involved in centrosome separation

¹ Departments of Biological Sciences, and Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA; ² Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA; ³ Department of Developmental Biology, and Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA; ⁴ Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; ⁵ Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA

β-Catenin plays important roles in cell adhesion and gene transcription, and has been shown recently to be essential for the establishment of a bipolar mitotic spindle. Here we show that β-catenin is a component of interphase centrosomes and that stabilization of β-catenin, mimicking mutations found in cancers, induces centrosome splitting. Centrosomes are held together by a dynamic linker regulated by Nek2 kinase and its substrates C-Nap1 (centrosomal Nek2-associated protein 1) and Rootletin. We show that β-catenin binds to and is phosphorylated by Nek2, and is in a complex with Rootletin. In interphase, β-catenin colocalizes with Rootletin between C-Nap1 puncta at the proximal end of centrioles, and this localization is dependent on C-Nap1 and Rootletin. In mitosis, when Nek2 activity increases, β-catenin localizes to centrosomes at spindle poles independent of Rootletin. Increased Nek2 activity disrupts the interaction of Rootletin with centrosomes and results in binding of β-catenin to Rootletin-independent sites on centrosomes, an event that is required for centrosome separation. These results identify β-catenin as a component of the intercentrosomal linker and define a new function for β-catenin as a key regulator of mitotic centrosome separation.

[Keywords: β-Catenin; centrosome; Nek2; mitosis; C-Nap1; Rootletin]]

Received July 23, 2007; revised version accepted November 2, 2007.

⁷ Present address: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.

⁸ Corresponding author.

E-MAIL angelab{at}stanford.edu; FAX (650) 724-4927.

Supplemental material is available at http://www.genesdev.org.

Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1596308

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