Kinase-regulated stabilization of beta-catenin at mitotic centrosomes
Abstract/Contents
- Abstract
- [Beta]-Catenin is a multifunctional protein with critical roles in cell-cell adhesion, Wnt-signaling and the centrosome cycle. Whereas the roles of [beta]-catenin in adhesion and Wnt-signaling are well understood, how [beta]-catenin regulates the centrosome cycle is not. NIMA-related protein kinase 2 (Nek2), which stimulates centrosome separation, binds to and phosphorylates [beta]-catenin. Using in vitro and cell-based assays, we show that Nek2 phosphorylates the same regulatory sites as Glycogen Synthase Kinase 3[beta] (GSK3[beta]) in the N-terminus of [beta]-catenin (S33/S37/T41) as well as additional sites. Significantly, Nek2, not GSK3[beta], is responsible for phosphorylating [beta]-catenin at centrosomes. Nek2 binding promotes [beta]-catenin stability by inhibiting binding of the E3 ligase [beta]-TrCP to [beta]-catenin, thereby preventing [beta]-catenin ubiquitination and degradation. Thus, [beta]-catenin phosphorylated by Nek2 on S33/S37/T41 accumulates at centrosomes in mitosis. We further show that Plk1 regulates Nek2 activity in stabilizing [beta]-catenin. Taken together, these results identify a novel mechanism for regulating [beta]-catenin stability, and provide new insight into a pathway involving Plk1, Nek2 and [beta]-catenin that regulates the centrosome cycle.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2013 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Mbom, Bertrade Clemence Ange |
|---|---|
| Associated with | Stanford University, Department of Biology. |
| Primary advisor | Nelson, W. J. (W. James) |
| Thesis advisor | Nelson, W. J. (W. James) |
| Thesis advisor | Stearns, Tim |
| Thesis advisor | Straight, Aaron, 1966- |
| Thesis advisor | Weis, William I |
| Advisor | Stearns, Tim |
| Advisor | Straight, Aaron, 1966- |
| Advisor | Weis, William I |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Bertrade Clemence Ange Mbom. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Ph.D. Stanford University 2013 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2013 by Bertrade Clemence Mbom
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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