Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 290, Issue 45, Pages 27053-27066Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M115.658534
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Funding
- Chinese 973 Project [2012CB917204, 2012CB945002, 2002CB713700]
- Anhui Province Key Project [08040102005]
- International Collaboration Grant [2009DFA31010]
- Chinese Natural Science Foundation [90508002, 31301120, 91129714, 31301121, 31071184, 81270466, 90913016, 31501095, MOE20113402130010]
- Fundamental Research Funds for Central Universities [WK2060190018]
- Anhui Provincial Natural Science Foundation [1508085SMC213]
- China Postdoctoral Science Foundation [2014M560517]
- National Institutes of Health [DK56292, CA164133, G12RR03034]
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Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochores. During chromosome alignment, kinetochore-bound microtubules undergo dynamic cycles between growth and shrinkage, leading to an oscillatory movement of chromosomes along the spindle axis. Although kinetochore protein CENP-H serves as a molecular control of kinetochore-microtubule dynamics, the mechanistic link between CENP-H and kinetochore microtubules (kMT) has remained less characterized. Here, we show that CSPP1 is a kinetochore protein essential for accurate chromosome movements in mitosis. CSPP1 binds to CENP-H in vitro and in vivo. Suppression of CSPP1 perturbs proper mitotic progression and compromises the satisfaction of spindle assembly checkpoint. In addition, chromosome oscillation is greatly attenuated in CSPP1-depleted cells, similar to what was observed in the CENP-H-depleted cells. Importantly, CSPP1 depletion enhances velocity of kinetochore movement, and overexpression of CSPP1 decreases the speed, suggesting that CSPP1 promotes kMT stability during cell division. Specific perturbation of CENP-H/CSPP1 interaction using a membrane-permeable competing peptide resulted in a transient mitotic arrest and chromosome segregation defect. Based on these findings, we propose that CSPP1 cooperates with CENP-H on kinetochores to serve as a novel regulator of kMT dynamics for accurate chromosome segregation.
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