科研之友
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摘要
beta-Catenin is a multifunctional protein with critical roles in cell-cell adhesion, Wnt signaling, and the centrosome cycle. Whereas the regulation of beta-catenin in cell-cell adhesion and Wnt signaling are well understood, how beta-catenin is regulated at the centrosome is not. NIMA-related protein kinase 2 (Nek2), which regulates centrosome disjunction/splitting, binds to and phosphorylates beta-catenin. Using in vitro and cell-based assays, we show that Nek2 phosphorylates the same regulatory sites in the N-terminus of beta-catenin as glycogen synthase kinase 3 beta (GSK3 beta), which are recognized by a specific phospho-S33/S37/T41 antibody, as well as additional sites. Nek2 binding to beta-catenin appears to inhibit binding of the E3 ligase beta-TrCP and prevents beta-catenin ubiquitination and degradation. Thus beta-catenin phosphorylated by Nek2 is stabilized and accumulates at centrosomes in mitosis. We further show that polo-like kinase 1 (Plk1) regulates Nek2 phosphorylation and stabilization of beta-catenin. Taken together, these results identify a novel mechanism for regulating beta-catenin stability that is independent of GSK3 beta and provide new insight into a pathway involving Plk1, Nek2, and beta-catenin that regulates the centrosome cycle.
- 出版日期2014-4-1
