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“……开始的结束”:细胞周期蛋白依赖性激酶1阈值与有丝分裂退出

'... The end of the beginning': cdk1 thresholds and exit from mitosis.

作者信息

Wolf Frank, Sigl Reinhard, Geley Stephan

机构信息

Biocenter, Division of Molecular Pathophysiology, Innsbruck Medical University, Innsbruck, Austria.

出版信息

Cell Cycle. 2007 Jun 15;6(12):1408-11. Epub 2007 Apr 27.

Abstract

Exit from mitosis requires the proteolytic degradation of mitotic cyclins, which is instigated by the APC/C ubiquitin ligase. The coincidence of mitotic cyclin B1 degradation with the onset of anaphase intuitively suggested a requirement of cyclin degradation for sister chromatid separation. While this hypothesis has originally been refuted, evidence that cyclin B1 degradation is required for anaphase during meiosis has been obtained, while its requirement for anaphase during mitosis is still more controversial. By studying human cells engineered to express nondegradable cyclin B1, we have recently shown that stable cyclin B1 affects progression through mitosis at various steps in a dose-dependent manner. These experiments suggest that controlled exit from mitosis might involve CDK activity thresholds for important late mitotic events, such as the onset of anaphase, formation of the spindle midzone, the onset of cytokinesis, cellular abscission and chromosome decondensation.

摘要

从有丝分裂中退出需要有丝分裂周期蛋白的蛋白水解降解,这是由后期促进复合体/细胞周期体(APC/C)泛素连接酶启动的。有丝分裂周期蛋白B1的降解与后期开始同时发生,直观地表明姐妹染色单体分离需要周期蛋白降解。虽然这一假设最初被否定,但现已获得证据表明减数分裂过程中后期需要周期蛋白B1降解,而其在有丝分裂后期的必要性仍更具争议性。通过研究经基因工程改造以表达不可降解周期蛋白B1的人类细胞,我们最近表明稳定的周期蛋白B1以剂量依赖的方式在有丝分裂的各个步骤影响进程。这些实验表明,有丝分裂的受控退出可能涉及重要有丝分裂后期事件的CDK活性阈值,如后期开始、纺锤体中间区形成、胞质分裂开始、细胞脱离和染色体解聚。

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