Dishevelled, a Wnt signalling component, is involved in mitotic progression in cooperation with Plk1. EMBO J

Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.
The EMBO Journal (Impact Factor: 10.43). 10/2010; 29(20):3470-83. DOI: 10.1038/emboj.2010.221
Source: PubMed


Wnt signalling is known to promote G1/S progression through the stimulation of gene expression, but whether this signalling regulates mitotic progression is not clear. Here, the function of dishevelled 2 (Dvl2), which transmits the Wnt signal, in mitosis was examined. Dvl2 localized to the spindles and spindle poles during mitosis. When cells were treated with nocodazole, Dvl2 was observed at the kinetochores (KTs). Dvl2 bound to and was phosphorylated at Thr206 by a mitotic kinase, Polo-like kinase 1 (Plk1), and this phosphorylation was required for spindle orientation and stable microtubule (MT)-KT attachment. Dvl2 was also found to be involved in the activation of a spindle assembly checkpoint (SAC) kinase, Mps1, and the recruitment of other SAC components, Bub1 and BubR1, to the KTs. However, the phosphorylation of Dvl2 by Plk1 was dispensable for SAC. Furthermore, Wnt receptors were involved in spindle orientation, but not in MT-KT attachment or SAC. These results suggested that Dvl2 is involved in mitotic progression by regulating the dynamics of MT plus-ends and the SAC in Plk1-dependent and -independent manners.

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    • "Here we suggest one possibility for Nkd2 mechanism in mitosis. Dvl2, whose antagonist is NKD in WNT pathway, is involved in mitotic progression in cooperation with Plk1 (Kikuchi et al. 2010). Phosphorylation of Dvl2 by Plk1 is dispensable for activation of Spindle Assembly Checkpoint (SAC). "
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    • "Additionally, Axin phosphorylation by Plk1 is essential for proper centrosome function (Ruan et al., 2012). Plk1 also phosphorylates Disheveled 2 (Dvl2), a central component of the Wnt signaling pathway that plays a role in SAC activation by recruiting SAC components Mps1, Bub1, and BubR1 to kinetochores (Kikuchi et al., 2010). In addition to conductin and Dvl2, both GSK3β and β-catenin have been shown to be involved in centrosome separation and to regulate spindle microtubules during mitosis (Wakefield et al., 2003; Kaplan et al., 2004; Bobinnec et al., 2006; Bahmanyar et al., 2008). "
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    • "The roles of these extra-centrosomes as well as the fate of the cells with multi-centrosomes require further investigation and could provide insight into a new mechanism for tumor formation and cancer development. It is intriguing to note that another component in Wnt signaling, Dvl2, is also phosphorylated by PLK1 [26]. Together with the report that PLK1 is overexpressed in colorectal cancers, the majority of which are characterized by dysregulated Wnt signalling [27], it is of interest to test whether PLK1 plays a role in regulating Wnt/β-catenin signalling in the future. "
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