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纺锤体装配检查点和 Polo 激酶的空间激活决定了细胞分裂的持续时间,并防止肿瘤形成。

The spindle assembly checkpoint and the spatial activation of Polo kinase determine the duration of cell division and prevent tumor formation.

机构信息

Univ Rennes, CNRS, INSERM, IGDR (Institut de Génétique et Développement de Rennes) UMR 6290, ERL U1305, Rennes, France.

Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Quebec, Canada.

出版信息

PLoS Genet. 2022 Apr 4;18(4):e1010145. doi: 10.1371/journal.pgen.1010145. eCollection 2022 Apr.

Abstract

The maintenance of a restricted pool of asymmetrically dividing stem cells is essential for tissue homeostasis. This process requires the control of mitotic progression that ensures the accurate chromosome segregation. In addition, this event is coupled to the asymmetric distribution of cell fate determinants in order to prevent stem cell amplification. How this coupling is regulated remains poorly described. Here, using asymmetrically dividing Drosophila neural stem cells (NSCs), we show that Polo kinase activity levels determine timely Cyclin B degradation and mitotic progression independent of the spindle assembly checkpoint (SAC). This event is mediated by the direct phosphorylation of Polo kinase by Aurora A at spindle poles and Aurora B kinases at centromeres. Furthermore, we show that Aurora A-dependent activation of Polo is the major event that promotes NSC polarization and together with the SAC prevents brain tumor growth. Altogether, our results show that an Aurora/Polo kinase module couples NSC mitotic progression and polarization for tissue homeostasis.

摘要

维持有限的不对称分裂干细胞池对于组织稳态至关重要。这个过程需要控制有丝分裂进程,以确保染色体的准确分离。此外,这个事件与细胞命运决定因素的不对称分布相偶联,以防止干细胞扩增。这种偶联是如何调节的仍描述得很差。在这里,我们使用不对称分裂的果蝇神经干细胞(NSCs),表明 Polo 激酶活性水平决定了细胞周期蛋白 B 的及时降解和有丝分裂进程,而与纺锤体组装检查点(SAC)无关。这个事件是由 Aurora A 在纺锤体两极和 Aurora B 激酶在着丝粒处直接磷酸化 Polo 激酶介导的。此外,我们还表明,Aurora A 依赖性 Polo 的激活是促进 NSC 极化的主要事件,与 SAC 一起防止脑肿瘤生长。总之,我们的结果表明,Aurora/Polo 激酶模块将 NSC 的有丝分裂进程和极化偶联起来,以维持组织稳态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63ef/9009772/b5c7a9d1e451/pgen.1010145.g001.jpg

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