Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation
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作者:
Tsukahara, Tatsuya
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Univ Tokyo, Grad Sch Sci, Grad Program Biophys & Biochem, Tokyo 1130032, Japan
Univ Tokyo, Inst Mol & Cellular Biosci, Lab Chromosome Dynam, Tokyo 1130032, JapanUniv Tokyo, Grad Sch Sci, Grad Program Biophys & Biochem, Tokyo 1130032, Japan
Tsukahara, Tatsuya
[1
,2
]
Tanno, Yuji
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Univ Tokyo, Inst Mol & Cellular Biosci, Lab Chromosome Dynam, Tokyo 1130032, JapanUniv Tokyo, Grad Sch Sci, Grad Program Biophys & Biochem, Tokyo 1130032, Japan
Tanno, Yuji
[2
]
Watanabe, Yoshinori
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Univ Tokyo, Grad Sch Sci, Grad Program Biophys & Biochem, Tokyo 1130032, Japan
Univ Tokyo, Inst Mol & Cellular Biosci, Lab Chromosome Dynam, Tokyo 1130032, JapanUniv Tokyo, Grad Sch Sci, Grad Program Biophys & Biochem, Tokyo 1130032, Japan
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
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.
机构:
Natl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Yasukawa, Mami
Ando, Yoshinari
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Natl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Ando, Yoshinari
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Yamashita, Taro
Matsuda, Yoko
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Tokyo Metropolitan Geriatr Hosp, Dept Pathol, Tokyo 1730015, Japan
Inst Gerontol, Tokyo 1730015, Japan
Kagawa Univ, Oncol Pathol, Dept Pathol & Host Def, Takamatsu, Kagawa 7610793, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Matsuda, Yoko
Shoji, Shisako
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RIKEN, Lab Prot Funct & Struct Biol, Ctr Biosyst Dynam Res, Yokohama, Kanagawa 2300045, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Shoji, Shisako
Morioka, Masaki Suimye
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RIKEN, Ctr Integrat Med Sci, Prevent Med & Appl Genom Unit, Yokohama, Kanagawa 2300045, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Morioka, Masaki Suimye
Kawaji, Hideya
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RIKEN, Ctr Integrat Med Sci, Prevent Med & Appl Genom Unit, Yokohama, Kanagawa 2300045, Japan
RIKEN, Prevent Med & Diag Innovat Program, Wako, Saitama 3510198, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Kawaji, Hideya
Shiozawa, Kumiko
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Natl Canc Ctr, Div Rare Canc Res, Tokyo 1040045, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Shiozawa, Kumiko
Machitani, Mitsuhiro
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Natl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Machitani, Mitsuhiro
Abe, Takaya
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RIKEN, Ctr Life Sci Technol, Anim Resource Dev Unit, Kobe, Hyogo 6500047, Japan
RIKEN, Ctr Life Sci Technol, Genet Engn Team, Kobe, Hyogo 6500047, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Abe, Takaya
Yamada, Shinji
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Tohoku Univ, Grad Sch Med, Dept Antibody Drug Dev, Sendai, Miyagi 9808575, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Yamada, Shinji
Kaneko, Mika K.
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Tohoku Univ, Grad Sch Med, Dept Antibody Drug Dev, Sendai, Miyagi 9808575, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Kaneko, Mika K.
Kato, Yukinari
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Tohoku Univ, Grad Sch Med, Dept Antibody Drug Dev, Sendai, Miyagi 9808575, Japan
Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 9808579, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Kato, Yukinari
Furuta, Yasuhide
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RIKEN, Ctr Life Sci Technol, Anim Resource Dev Unit, Kobe, Hyogo 6500047, Japan
RIKEN, Ctr Life Sci Technol, Genet Engn Team, Kobe, Hyogo 6500047, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Furuta, Yasuhide
Kondo, Tadashi
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Natl Canc Ctr, Div Rare Canc Res, Tokyo 1040045, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Kondo, Tadashi
Shirouzu, Mikako
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RIKEN, Lab Prot Funct & Struct Biol, Ctr Biosyst Dynam Res, Yokohama, Kanagawa 2300045, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Shirouzu, Mikako
Hayashizaki, Yoshihide
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RIKEN, Prevent Med & Diag Innovat Program, Wako, Saitama 3510198, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
Hayashizaki, Yoshihide
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Kaneko, Shuichi
Masutomi, Kenkichi
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Natl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, JapanNatl Canc Ctr, Div Canc Stem Cell, Tokyo 1040045, Japan
机构:
Cent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China
Hunan Prov Engn Res Ctr Translat Med & Innovat Dru, Changsha, Peoples R ChinaCent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China
Huang, Si
Xiao, Jingxian
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Hunan Univ Med, Sch Med Sci, Huaihua, Peoples R ChinaCent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China
Xiao, Jingxian
Wu, Junyong
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Cent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China
Hunan Prov Engn Res Ctr Translat Med & Innovat Dru, Changsha, Peoples R ChinaCent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China
Wu, Junyong
Liu, Jiayi
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Cent South Univ, Xiangya Hosp 2, Dept Radiol, Changsha, Peoples R ChinaCent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China
Liu, Jiayi
Feng, Xueping
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Cent South Univ, Xiangya Hosp, Inst Med Sci, Changsha, Peoples R ChinaCent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China
Feng, Xueping
Yang, Chengdong
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Cent South Univ, Xiangya Hosp 2, Dept Psychiat, Changsha, Peoples R ChinaCent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China
Yang, Chengdong
Xiang, Daxiong
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Cent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China
Hunan Prov Engn Res Ctr Translat Med & Innovat Dru, Changsha, Peoples R ChinaCent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China
Xiang, Daxiong
Luo, Shilin
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Cent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China
Hunan Prov Engn Res Ctr Translat Med & Innovat Dru, Changsha, Peoples R ChinaCent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha, Peoples R China
机构:
Natl Def Med Ctr, Grad Inst Life Sci, Taiwan Int Grad Program, Mol & Cell Biol Program, Taipei, Taiwan
Acad Sinica, Inst Mol Biol, Taipei, TaiwanNatl Def Med Ctr, Grad Inst Life Sci, Taiwan Int Grad Program, Mol & Cell Biol Program, Taipei, Taiwan
Su, Yee-Fun
Yang, Tsunghan
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Acad Sinica, Inst Mol Biol, Taipei, TaiwanNatl Def Med Ctr, Grad Inst Life Sci, Taiwan Int Grad Program, Mol & Cell Biol Program, Taipei, Taiwan
Yang, Tsunghan
Huang, Hoting
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机构:
Acad Sinica, Inst Mol Biol, Taipei, TaiwanNatl Def Med Ctr, Grad Inst Life Sci, Taiwan Int Grad Program, Mol & Cell Biol Program, Taipei, Taiwan
Huang, Hoting
Liu, Leroy F.
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Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USANatl Def Med Ctr, Grad Inst Life Sci, Taiwan Int Grad Program, Mol & Cell Biol Program, Taipei, Taiwan
Liu, Leroy F.
Hwang, Jaulang
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机构:
Natl Def Med Ctr, Grad Inst Life Sci, Taiwan Int Grad Program, Mol & Cell Biol Program, Taipei, Taiwan
Acad Sinica, Inst Mol Biol, Taipei, TaiwanNatl Def Med Ctr, Grad Inst Life Sci, Taiwan Int Grad Program, Mol & Cell Biol Program, Taipei, Taiwan