Kinase-regulated stabilization of beta-catenin at mitotic centrosomes
- Bertrade Clemence Ange Mbom.
- Aug. 2013.
- Physical description
- online resource (vii, 91 pages) : illustrations (some color)
- Mbom, Bertrade Clemence Ange.
- Nelson, W. J. (W. James) thesis advisor (primary).
- Stearns, Tim. thesis advisor.
- Straight, Aaron, 1966- thesis advisor.
- Weis, William I. thesis advisor.
- Stanford University. Department of Biology.
- Stanford University. Committee on Graduate Studies. degree grantor.
- Includes bibliographical references.
- [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.
- Cell Cycle > physiology
- Centrosome > metabolism
- Mitosis > genetics
- beta Catenin > metabolism
- Cell Adhesion
- Glycogen Synthase Kinase 3 > metabolism
- Protein-Serine-Threonine Kinases > metabolism
- Publication date
- Title Variation
- Kinase-regulated stabilization of β-catenin at mitotic centrosomes
- Submitted to the Department of Biology and the Committee on Graduate Studies of Stanford University.
- Thesis (Ph.D.)--Stanford University, 2013.