期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 294, 期 6, 页码 2021-2035出版社
ELSEVIER
DOI: 10.1074/jbc.RA118.005978
关键词
centromere; mitosis; kinetochore; cell cycle; histone modification; chromosomal passenger complex; cohesin; Haspin; heterochromatin protein 1; sister chromatid cohesion; Aurora B; INCENP
资金
- National Key Research and Development Program of China [2017YFA0503600]
- National Natural Science Foundation of China (NSFC) [31571393, 31771499, 31561130155, 31322032, 31371359]
- Natural Science Foundation of Zhejiang Province [LZ19C070001, LR13C070001, LY17C070003]
- Newton Advanced Fellowship [NA140075]
- Fundamental Research Funds for the Central Universities
The chromosomal passenger complex (CPC) is a master regulator of mitosis. CPC consists of inner centromere protein (INCENP), Survivin, Borealin, and the kinase Aurora B and plays key roles in regulating kinetochore-microtubule attachments and spindle assembly checkpoint signaling. However, the role of CPC in sister chromatid cohesion, mediated by the cohesin complex, remains incompletely understood. Here, we show that Aurora B kinase activity contributes to centromeric cohesion protection partly through promoting kinetochore localization of the kinase Bub1. Interestingly, disrupting the interaction of INCENP with heterochromatin protein 1 (HP1) in HeLa cells selectively weakens cohesion at mitotic centromeres without detectably reducing the kinase activity of Aurora B. Thus, through this INCENP-HP1 interaction, the CPC also protects centromeric cohesion independently of Aurora B kinase activity. Moreover, the requirement for the INCENP-HP1 interaction in centromeric cohesion protection can be bypassed by tethering HP1 to centromeres or by depleting the cohesin release factor Wapl. We provide further evidence suggesting that the INCENP-HP1 interaction protects centromeric cohesion by promoting the centromere localization of Haspin, a protein kinase that antagonizes Wapl activity at centromeres. Taken together, this study identifies Aurora B kinase activity-dependent and -independent roles for the CPC in regulating centromeric cohesion during mitosis in human cells.
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