beta-Catenin is a Nek2 substrate involved in centrosome separation.

Genes Dev 2008 Jan 17;22(1):91-105. Epub 2007 Dec 17.

Department of Biological Sciences, Stanford University, Stanford, California 94305, USA.

beta-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 beta-catenin is a component of interphase centrosomes and that stabilization of beta-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 beta-catenin binds to and is phosphorylated by Nek2, and is in a complex with Rootletin. In interphase, beta-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, beta-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 beta-catenin to Rootletin-independent sites on centrosomes, an event that is required for centrosome separation. These results identify beta-catenin as a component of the intercentrosomal linker and define a new function for beta-catenin as a key regulator of mitotic centrosome separation.

Download full-text PDF

Source
http://dx.doi.org/10.1101/gad.1596308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151018PMC
January 2008
8 Reads

Publication Analysis

Top Keywords

centrosome separation
12
beta-catenin
10
nek2 activity
8
beta-catenin component
8
rootletin
6
centrosomes
5
rootletin-independent sites
4
c-nap1 centrosomal
4
sites centrosomes
4
centrosomal nek2-associated
4
nek2-associated protein
4
beta-catenin binds
4
rootletin beta-catenin
4
protein rootletin
4
substrates c-nap1
4
beta-catenin localizes
4
dynamic linker
4
localizes centrosomes
4
held dynamic
4
event required
4

Similar Publications