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Uncoupling of the spindle-checkpoint and chromosome-congression functions of BubR1
Elowe, Sabine1; Dulla, Kalyan1; Uldschmid, Andreas1; Li, Xiuling2; Dou, Zhen1; Nigg, Erich A.1,3; Sabine Elowe
关键词Bubr1 Chromosome Congression Kinetochore Mitosis Spindle Checkpoint
刊名JOURNAL OF CELL SCIENCE
2010
DOI10.1242/jcs.056507
123期:1页:84-94
收录类别SCI
文章类型Article
部门归属18
项目归属1803
产权排名2;4
WOS标题词Science & Technology ; Life Sciences & Biomedicine
类目[WOS]Cell Biology
研究领域[WOS]Cell Biology
关键词[WOS]MITOTIC CHECKPOINT ; ASSEMBLY CHECKPOINT ; PROTEIN BUBR1 ; PSEUDOSUBSTRATE INHIBITOR ; UNATTACHED KINETOCHORES ; ALIGNMENT ; ANAPHASE ; CDC20 ; MAD2 ; MITOSIS
英文摘要The BubR1 checkpoint protein performs multiple functions in mitosis. We have carried out a functional analysis of conserved motifs of human BubR1 (also known as BUB1B) and demonstrate that spindle assembly checkpoint ( SAC) and chromosome attachment functions can be uncoupled from each other. Mutation of five proline-directed serine phosphorylation sites, identified in vivo by mass spectrometry, essentially abolishes attachment of chromosomes to the spindle but has no effect on SAC functionality. By contrast, mutation of the two conserved KEN boxes required for SAC function does not impact chromosome congression. Interestingly, the contribution of the two KEN-box motifs is not equal. Cdc20 associates with the N-terminal but not C-terminal KEN box, and mutation of the N-terminal KEN motif results in more severe acceleration of mitotic timing. Moreover, the two KEN motifs are not sufficient for maximal binding of Cdc20 and APC/C, which also requires sequences in the BubR1 C-terminus. Finally, mutation of the GLEBS motif causes loss of Bub3 interaction and mislocalization of BubR1 from the kinetochore; concomitantly, BubR1 phosphorylation as well as SAC activity and chromosome congression are impaired, indicating that the GLEBS motif is strictly required for both major functions of human BubR1.
语种英语
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WOS记录号WOS:000272839800010
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文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/102847
专题中国科学院大连化学物理研究所
通讯作者Sabine Elowe
作者单位1.Max Planck Inst Biochem, Dept Cell Biol, D-82152 Martinsried, Germany
2.Chinese Acad Sci, Dalian Inst Chem Phys, Grp 1803, Dalian 116023, Peoples R China
3.Univ Basel, Biozentrum, CH-4056 Basel, Switzerland
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Elowe, Sabine,Dulla, Kalyan,Uldschmid, Andreas,et al. Uncoupling of the spindle-checkpoint and chromosome-congression functions of BubR1[J]. JOURNAL OF CELL SCIENCE,2010,123(1):84-94.
APA Elowe, Sabine.,Dulla, Kalyan.,Uldschmid, Andreas.,Li, Xiuling.,Dou, Zhen.,...&Sabine Elowe.(2010).Uncoupling of the spindle-checkpoint and chromosome-congression functions of BubR1.JOURNAL OF CELL SCIENCE,123(1),84-94.
MLA Elowe, Sabine,et al."Uncoupling of the spindle-checkpoint and chromosome-congression functions of BubR1".JOURNAL OF CELL SCIENCE 123.1(2010):84-94.
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