Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation

被引:190
|
作者
Tsukahara, Tatsuya [1 ,2 ]
Tanno, Yuji [2 ]
Watanabe, Yoshinori [1 ,2 ]
机构
[1] Univ Tokyo, Grad Sch Sci, Grad Program Biophys & Biochem, Tokyo 1130032, Japan
[2] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Chromosome Dynam, Tokyo 1130032, Japan
关键词
SISTER-CHROMATID COHESION; FISSION YEAST; CELL-DIVISION; SCHIZOSACCHAROMYCES-POMBE; AURORA-B; MICROTUBULE ATTACHMENT; PASSENGER COMPLEX; INNER CENTROMERE; MITOTIC SPINDLE; MEIOSIS-I;
D O I
10.1038/nature09390
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Successful partition of replicated genomes at cell division requires chromosome attachment to opposite poles of mitotic spindle (bi-orientation). Any defects in this regulation bring about chromosomal instability, which may accelerate tumour progression in humans. To achieve chromosome bi-orientation at prometaphase, the chromosomal passenger complex (CPC), composed of catalytic kinase Aurora B and regulatory components (INCENP, Survivin and Borealin), must be localized to centromeres to phosphorylate kinetochore substrates(1-7). Although the CPC dynamically changes the subcellular localization, the regulation of centromere targeting is largely unknown(1). Here we isolated a fission yeast cyclin B mutant defective specifically in chromosome bi-orientation. Accordingly, we identified Cdk1 (also known as Cdc2)-cyclin-B-dependent phosphorylation of Survivin. Preventing Survivin phosphorylation impairs centromere CPC targeting as well as chromosome bi-orientation, whereas phosphomimetic Survivin suppresses the bi-orientation defect in the cyclin B mutant. Survivin phosphorylation promotes direct binding with shugoshin(8,9), which we now define as a conserved centromeric adaptor of the CPC. In human cells, the phosphorylation of Borealin has a comparable role. Thus, our study resolves the conserved mechanisms of CPC targeting to centromeres, highlighting a key role of Cdk1-cyclin B in chromosome bi-orientation.
引用
收藏
页码:719 / U111
页数:7
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