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Dev Cell. 2014 Feb 10;28(3):268-81. doi: 10.1016/j.devcel.2013.12.013. Epub 2014 Jan 23.

A microtubule-associated zinc finger protein, BuGZ, regulates mitotic chromosome alignment by ensuring Bub3 stability and kinetochore targeting.

Author information

1
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Embryology, Carnegie Institution for Science, 3520 San Martin Dr., Baltimore, MD 21218, USA.
2
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
3
Department of Embryology, Carnegie Institution for Science, 3520 San Martin Dr., Baltimore, MD 21218, USA.
4
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
5
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: xlzhu@sibcb.ac.cn.
6
Department of Embryology, Carnegie Institution for Science, 3520 San Martin Dr., Baltimore, MD 21218, USA. Electronic address: zheng@ciwemb.edu.

Abstract

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 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 BuGZ not only serves as a molecular chaperone for Bub3 but also enhances its loading onto kinetochores during prometaphase in a microtubule-dependent manner to promote chromosome alignment.

PMID:
24462186
PMCID:
PMC3927447
DOI:
10.1016/j.devcel.2013.12.013
[Indexed for MEDLINE]
Free PMC Article

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