A Microtubule-Associated Zinc Finger Protein, BuGZ, Regulates Mitotic Chromosome Alignment by Ensuring Bub3 Stability and Kinetochore Targeting

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• 作者：Hao Jiang ; Xiaonan He ; Shusheng Wang ; Junling Jia ; Yihan Wan ; Yueju Wang ; Rong Zeng ; John Yates III ; Xueliang Zhu ; Yixian Zheng
• 刊名：Developmental Cell
• 出版年：10 February, 2014
• 年：2014
• 卷：28
• 期：3
• 页码：268-281
• 全文大小：5131 K

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Summary

Equal chromosome segregation requires proper assembly of many proteins, including Bub3, onto kinetochores to promote kinetochore-microtubule interactions. By screening for mitotic regulators in the spindle envelope and matrix (Spemix), we identify a conserved Bub3 interacting and GLE-2-binding sequence (GLEBS) containing ZNF207 (BuGZ) that associates with spindle microtubules and regulates聽chromosome alignment. Using its conserved GLEBS, BuGZ directly binds and stabilizes Bub3. BuGZ also uses its microtubule-binding domain to enhance the loading of Bub3 to kinetochores that have assumed initial interactions with microtubules in prometaphase. This enhanced Bub3 loading is required for proper chromosome alignment and metaphase to anaphase progression. Interestingly, we show that microtubules are required for the highest kinetochore loading of Bub3, BubR1, and CENP-E during prometaphase. These findings suggest that聽BuGZ not only serves as a molecular chaperone for聽Bub3 but also enhances its loading onto kinetochores during prometaphase in a microtubule-dependent manner to promote chromosome alignment.