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APC/CCdh1 is required for the termination of chromosomal passenger complex activity upon mitotic exit.
Journal of Cell Science ( IF 3.3 ) Pub Date : 2020-09-15 , DOI: 10.1242/jcs.251314
Takaaki Tsunematsu 1 , Rieko Arakaki 1 , Hidehiko Kawai 2 , Jan Ruppert 3 , Koichi Tsuneyama 4 , Naozumi Ishimaru 1 , William C Earnshaw 3 , Michele Pagano 5, 6, 7 , Yasusei Kudo 8, 9
Affiliation  

Takaaki Tsunematsu, Rieko Arakaki, Hidehiko Kawai, Jan Ruppert, Koichi Tsuneyama, Naozumi Ishimaru, William C. Earnshaw, Michele Pagano, and Yasusei Kudo

During mitosis, the chromosomal passenger complex (CPC) ensures the faithful transmission of the genome. The CPC is composed of the enzymatic component Aurora B (AURKB) and the three regulatory and targeting components borealin, INCENP, and survivin (also known as BIRC5). Although the CPC is known to be involved in diverse mitotic events, it is still unclear how CPC function terminates after mitosis. Here we show that borealin is ubiquitylated by the anaphase promoting complex/cyclosome (APC/C) and its cofactor Cdh1 (also known as FZR1) and is subsequently degraded in G1 phase. Cdh1 binds to regions within the N terminus of borealin that act as a non-canonical degron. Aurora B has also been shown previously to be degraded by the APC/CCdh1 from late mitosis to G1. Indeed, Cdh1 depletion sustains an Aurora B activity with stable levels of borealin and Aurora B throughout the cell cycle, and causes reduced efficiency of DNA replication after release from serum starvation. Notably, inhibition of Aurora B kinase activity improves the efficiency of DNA replication in Cdh1-depleted cells. We thus propose that APC/CCdh1 terminates CPC activity upon mitotic exit and thereby contributes to proper control of DNA replication.



中文翻译:

APC/CCdh1 是在有丝分裂退出时终止染色体乘客复合物活动所必需的。

Takaaki Tsunematsu、Rieko Arakaki、Hidehiko Kawai、Jan Ruppert、Koichi Tsuneyama、Naozumi Ishimaru、William C. Earnshaw、Michele Pagano 和 Yasusei Kudo

在有丝分裂期间,染色体乘客复合体 (CPC) 确保基因组的忠实传递。CPC 由酶成分 Aurora B (AURKB) 和三种调节和靶向成分 borealin、INCENP 和 survivin(也称为 BIRC5)组成。尽管已知 CPC 参与多种有丝分裂事件,但仍不清楚有丝分裂后 CPC 功能如何终止。在这里,我们表明,borealin 被后期促进复合物/环体 (APC/C) 及其辅因子 Cdh1(也称为 FZR1)泛素化,随后在 G1 期降解。Cdh1 与作为非规范 degron 的 borealin N 末端内的区域结合。Aurora B 之前也已被证明会被 APC/C Cdh1降解从晚期有丝分裂到 G1。事实上,Cdh1 耗竭维持 Aurora B 活性,在整个细胞周期中保持稳定的 borealin 和 Aurora B 水平,并导致血清饥饿释放后 DNA 复制效率降低。值得注意的是,Aurora B 激酶活性的抑制提高了 Cdh1 耗尽细胞中 DNA 复制的效率。因此,我们建议 APC/C Cdh1在有丝分裂退出时终止 CPC 活性,从而有助于适当控制 DNA 复制。

更新日期:2020-10-02
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