Phosphorylation of Microtubule-binding Protein Hec1 by Mitotic Kinase Aurora B Specifies Spindle Checkpoint Kinase Mps1 Signaling at the Kinetochore |
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Authors: | Tongge Zhu Zhen Dou Bo Qin Changjiang Jin Xinghui Wang Leilei Xu Zhaoyang Wang Lijuan Zhu Fusheng Liu Xinjiao Gao Yuwen Ke Zhiyong Wang Felix Aikhionbare Chuanhai Fu Xia Ding Xuebiao Yao |
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Institution: | From the ‡Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei 230026, China.;the §Molecular Imaging Center, Morehouse School of Medicine, Atlanta, Georgia 30310, and ;¶Beijing University of Chinese Medicine, School of Graduate Studies, Beijing 100029, China |
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Abstract: | The spindle assembly checkpoint (SAC) is a quality control device to ensure accurate chromosome attachment to spindle microtubule for equal segregation of sister chromatid. Aurora B is essential for SAC function by sensing chromosome bi-orientation via spatial regulation of kinetochore substrates. However, it has remained elusive as to how Aurora B couples kinetochore-microtubule attachment to SAC signaling. Here, we show that Hec1 interacts with Mps1 and specifies its kinetochore localization via its calponin homology (CH) domain and N-terminal 80 amino acids. Interestingly, phosphorylation of the Hec1 by Aurora B weakens its interaction with microtubules but promotes Hec1 binding to Mps1. Significantly, the temporal regulation of Hec1 phosphorylation orchestrates kinetochore-microtubule attachment and Mps1 loading to the kinetochore. Persistent expression of phosphomimetic Hec1 mutant induces a hyperactivation of SAC, suggesting that phosphorylation-elicited Hec1 conformational change is used as a switch to orchestrate SAC activation to concurrent destabilization of aberrant kinetochore attachment. Taken together, these results define a novel role for Aurora B-Hec1-Mps1 signaling axis in governing accurate chromosome segregation in mitosis. |
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Keywords: | Checkpoint Control Kinetochore Mitosis Mitotic Spindle Phosphorylation Cenp-e Checkpoint |
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