期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 288, 期 50, 页码 36149-36159出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.507970
关键词
Checkpoint Control; Kinetochore; Mitosis; Mitotic Spindle; Phosphorylation; Cenp-e; Checkpoint
资金
- National Institutes of Health [DK56292, CA164133, 8G12MD007602, G12RR03034]
- Chinese 973 Project [2010CB912103, 2012CB917204, 2014CB964800]
- Anhui Province Key Project [08040102005]
- International Collaboration Grant [2009DFA31010]
- Chinese Natural Science Foundation [90508002, 91129714, 81270466, 90913016, 31000602, 31071184, 31171300, 31271439]
- Ministry of Education [20113402130010, WK2060190018, WK2340000021]
Background: Hec1 is a core component of outer kinetochore essential for chromosome segregation in mitosis. Results: Hec1 interacts with mitotic checkpoint kinase Mps1, and phosphorylation of Hec1 by Aurora B recruits Mps1 to kinetochore. Conclusion: Phosphorylation of Hec1 by Aurora B specifies Mps1 signaling at the kinetochore. Significance: Aurora B-Hec1-Mps1 axis orchestrates chromosome dynamics and stability in mitosis. The spindle assembly checkpoint (SAC) is a quality control device to ensure accurate chromosome attachment to spindle microtubule for equal segregation of sister chromatid. Aurora B is essential for SAC function by sensing chromosome bi-orientation via spatial regulation of kinetochore substrates. However, it has remained elusive as to how Aurora B couples kinetochore-microtubule attachment to SAC signaling. Here, we show that Hec1 interacts with Mps1 and specifies its kinetochore localization via its calponin homology (CH) domain and N-terminal 80 amino acids. Interestingly, phosphorylation of the Hec1 by Aurora B weakens its interaction with microtubules but promotes Hec1 binding to Mps1. Significantly, the temporal regulation of Hec1 phosphorylation orchestrates kinetochore-microtubule attachment and Mps1 loading to the kinetochore. Persistent expression of phosphomimetic Hec1 mutant induces a hyperactivation of SAC, suggesting that phosphorylation-elicited Hec1 conformational change is used as a switch to orchestrate SAC activation to concurrent destabilization of aberrant kinetochore attachment. Taken together, these results define a novel role for Aurora B-Hec1-Mps1 signaling axis in governing accurate chromosome segregation in mitosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据