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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
KeywordBubr1 Chromosome Congression Kinetochore Mitosis Spindle Checkpoint
Source PublicationJOURNAL OF CELL SCIENCE
2010
DOI10.1242/jcs.056507
Volume123Issue:1Pages:84-94
Indexed BySCI
SubtypeArticle
Department18
Funding Project1803
Contribution Rank2;4
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectCell Biology
WOS Research AreaCell Biology
WOS KeywordMITOTIC CHECKPOINT ; ASSEMBLY CHECKPOINT ; PROTEIN BUBR1 ; PSEUDOSUBSTRATE INHIBITOR ; UNATTACHED KINETOCHORES ; ALIGNMENT ; ANAPHASE ; CDC20 ; MAD2 ; MITOSIS
AbstractThe 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.
Language英语
URL查看原文
WOS IDWOS:000272839800010
Citation statistics
Cited Times:72[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/102847
Collection中国科学院大连化学物理研究所
Corresponding AuthorSabine Elowe
Affiliation1.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
Recommended Citation
GB/T 7714
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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