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Dishevelled,a Wnt signalling component,is involved in mitotic progression in cooperation with Plk1
Authors:Koji Kikuchi  Yohei Niikura  Katsumi Kitagawa  Akira Kikuchi
Institution:1. Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan;2. Center for Childhood Cancer, The Research Institute, Nationwide Children's Hospital, Columbus, OH, USA
Abstract: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.
Keywords:dishevelled  microtubule plus end  mitosis  Plk1  Wnt signalling
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