DOI | 10.1038/s41586-020-2187-y
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| Separase-triggered apoptosis enforces minimal length of mitosis |
| Iino, Yusuke1,2; Sawada, Takeshi1,2; Yamaguchi, Kenji1,2; Tajiri, Mio1,2; Ishii, Shin2,3; Kasai, Haruo1,2; Yagishita, Sho1,2
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| 2020-03-18
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发表期刊 | NATURE
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ISSN | 0028-0836
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EISSN | 1476-4687
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出版年 | 2020
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卷号 | 580期号:7804页码:542-+ |
文章类型 | Article
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语种 | 英语
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国家 | Germany |
英文关键词 | Prolonged mitosis often results in apoptosis(1). Shortened mitosis causes tumorigenic aneuploidy, but it is unclear whether it also activates the apoptotic machinery(2). Separase, a cysteine protease and trigger of all eukaryotic anaphases, has a caspase-like catalytic domain but has not previously been associated with cell death(3,4). Here we show that human cells that enter mitosis with already active separase rapidly undergo death in mitosis owing to direct cleavage of anti-apoptotic MCL1 and BCL-XL by separase. Cleavage not only prevents MCL1 and BCL-XL from sequestering pro-apoptotic BAK, but also converts them into active promoters of death in mitosis. Our data strongly suggest that the deadliest cleavage fragment, the C-terminal half of MCL1, forms BAK/BAX-like pores in the mitochondrial outer membrane. MCL1 and BCL-XL are turned into separase substrates only upon phosphorylation by NEK2A. Early mitotic degradation of this kinase is therefore crucial for preventing apoptosis upon scheduled activation of separase in metaphase. Speeding up mitosis by abrogation of the spindle assembly checkpoint results in a temporal overlap of the enzymatic activities of NEK2A and separase and consequently in cell death. We propose that NEK2A and separase jointly check on spindle assembly checkpoint integrity and eliminate cells that are prone to chromosome missegregation owing to accelerated progression through early mitosis.
If early mitosis is too short, separase induces apoptosis by cleaving MCL2 and BCL-XL, thereby eliminating cells that are prone to chromosome missegregation.
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领域 | 地球科学
; 气候变化
; 资源环境
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收录类别 | SCI-E
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WOS记录号 | WOS:000526470900002
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WOS关键词 | MITOCHONDRIAL OUTER-MEMBRANE
; SPINDLE ASSEMBLY CHECKPOINT
; SISTER-CHROMATID COHESION
; CELL-DEATH
; CANCER-CELLS
; BH3 DOMAINS
; BAX
; INHIBITION
; MCL-1
; OLIGOMERIZATION
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WOS类目 | Multidisciplinary Sciences
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WOS研究方向 | Science & Technology - Other Topics
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引用统计 |
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文献类型 | 期刊论文
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条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/281348
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专题 | 地球科学 资源环境科学 气候变化
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作者单位 | 1.Univ Tokyo, Ctr Dis Biol & Integrat Med, Fac Med, Lab Struct Physiol, Tokyo, Japan; 2.Univ Tokyo, Int Res Ctr Neurointelligence WPI IRCN, Tokyo, Japan; 3.Kyoto Univ, Grad Sch Informat, Kyoto, Japan
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推荐引用方式 GB/T 7714 |
Iino, Yusuke,Sawada, Takeshi,Yamaguchi, Kenji,et al. Separase-triggered apoptosis enforces minimal length of mitosis[J].
NATURE,2020,580(7804):542-+.
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APA |
Iino, Yusuke.,Sawada, Takeshi.,Yamaguchi, Kenji.,Tajiri, Mio.,Ishii, Shin.,...&Yagishita, Sho.(2020).Separase-triggered apoptosis enforces minimal length of mitosis.NATURE,580(7804),542-+.
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MLA |
Iino, Yusuke,et al."Separase-triggered apoptosis enforces minimal length of mitosis".NATURE 580.7804(2020):542-+.
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