期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep38791
关键词
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资金
- Chinese 973 Project [2012CB917204, 2014CB964803]
- Chinese Ministry of Science and Technology [2016YFA0100500]
- Chinese Natural Science Foundation [31621002, 31671405, 31501095, 31601097, 31471275, 31171300, 31301121]
- Anhui Provincial Natural Science Foundation [1508085SMC213]
- National Institutes of Health [CA164133, DK56292]
- Central University [WK2340000032, WK2340000021]
Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules. Our recent study shows SKAP is an EB1-dependent, microtubule plus-end tracking protein essential for kinetochore oscillations during mitosis. Here we show that phosphorylation of SKAP by GSK3 beta regulates Kif2b depolymerase activity by competing Kif2b for microtubule plus-end binding. SKAP is a bona fide substrate of GSK3 beta in vitro and the phosphorylation is essential for an accurate kinetochore-microtubule attachment in cells. The GSK3 beta-elicited phosphorylation sites were mapped by mass spectrometry and the phosphomimetic mutant of SKAP can rescue the phenotype of chromosome missegregation in SKAP-suppressed cells. Importantly, GSK3 beta-elicited phosphorylation promotes SKAP binding to Kif2b to regulate its depolymerase activity at the microtubule plus-ends. Based on those findings, we reason that GSK3 beta-SKAP-Kif2b signaling axis constitutes a dynamic link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division.
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