Mbom BC, Siemers KA, Ostrowski MA, Nelson WJ, Barth AI

β-Catenin is a multifunctional protein with critical roles in cell-cell adhesion, Wnt-signaling and the centrosome cycle. Whereas the regulation of β-catenin in cell-cell adhesion and Wnt-signaling are well understood, how β-catenin is regulated at the centrosome is not. NIMA-related protein kinase 2 (Nek2), which regulates centrosome disjunction/splitting, binds to and ...

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phosphorylates β-catenin. Using in vitro and cell-based assays, we show that Nek2 phosphorylates the same regulatory sites in the N-terminus of β-catenin as glycogen synthase kinase 3β (GSK3β), which are recognized by a specific phospho-S33/S37/T41 antibody, as well as additional sites. Nek2 binding to β-catenin appears to inhibit binding of the E3 ligase β-TrCP, and prevents β-catenin ubiquitination and degradation. Thus, β-catenin phosphorylated by Nek2 is stabilized and accumulates at centrosomes in mitosis. We further show that Plk1 regulates Nek2 phosphorylation and stabilization of β-catenin. Taken together, these results identify a novel mechanism for regulating β-catenin stability that is independent of GSK3β, and provide new insight into a pathway involving Plk1, Nek2 and β-catenin that regulates the centrosome cycle.

Date: Feb. 05, 2014

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