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极光激酶B(Aurora B)和染色体乘客复合体(INCENP)的共过表达严重扰乱有丝分裂,并显著改变整体转录格局。

Aurora B and INCENP co-overexpression severely disrupts mitosis and distinctly modifies the global transcriptional landscape.

作者信息

Galindo-Moreno María, Muñoz-Barrera Marta, Marcozzi Chiara, Bruno Federica, Maya-Álvarez Cristina, Cortés-Ledesma Felipe, Ríos Rosa María, González-Aguilera Cristina, Monje-Casas Fernando

机构信息

Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Spanish National Research Council (CSIC) - University of Seville - University Pablo de Olavide, Avda. Américo Vespucio, 24, 41092 Sevilla, Spain.

Topology and DNA Breaks Group, Spanish National Cancer Research Center (CNIO), c/ Melchor Fernández Almagro, 3, 28029 Madrid, Spain.

出版信息

iScience. 2025 May 22;28(6):112731. doi: 10.1016/j.isci.2025.112731. eCollection 2025 Jun 20.

DOI:10.1016/j.isci.2025.112731
PMID:40530423
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12172992/
Abstract

Aurora B kinase, as part of the chromosomal passenger complex (CPC), controls key processes during the cell cycle such as DNA compaction, genome partitioning, or cytokinesis. Nonetheless, increased Aurora B levels are a potential threat for the cells and have been linked to different tumor types. We have carried out an exhaustive characterization of the global consequences of the overexpression of Aurora B and INCENP, the scaffold of the CPC and an activator of Aurora B kinase activity, in non-transformed human cells. Our data demonstrate not only that an individual increase in the levels of Aurora B or INCENP have a different impact on the cells, but more importantly that their simultaneous overexpression stabilizes both CPC components, exacerbates Aurora B activity, severely impairs mitotic progression and chromosome dynamics, and has a distinctive and more dramatic effect on the transcriptional landscape of the cells.

摘要

极光激酶B(Aurora B kinase)作为染色体乘客复合体(chromosomal passenger complex, CPC)的一部分,在细胞周期中控制着诸如DNA压缩、基因组分配或胞质分裂等关键过程。尽管如此,极光激酶B水平的升高对细胞来说是一个潜在威胁,并且已与不同类型的肿瘤相关联。我们对极光激酶B和内着丝粒蛋白(INCENP,CPC的支架蛋白以及极光激酶B活性的激活剂)在未转化的人类细胞中过表达的整体后果进行了详尽的表征。我们的数据不仅表明极光激酶B或内着丝粒蛋白水平的单独升高对细胞有不同的影响,更重要的是,它们的同时过表达会使CPC的两个组分都稳定下来,加剧极光激酶B的活性,严重损害有丝分裂进程和染色体动态变化,并且对细胞的转录图谱有独特且更显著的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/987cc17b3835/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/e5f9dc07dbf0/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/a84424e8452b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/bbd0f0eb2dba/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/ab0ea85186be/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/ad4ad965fd02/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/8eeffce61299/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/987cc17b3835/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/e5f9dc07dbf0/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/a84424e8452b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/bbd0f0eb2dba/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/ab0ea85186be/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/ad4ad965fd02/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/8eeffce61299/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/12172992/987cc17b3835/gr6.jpg

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本文引用的文献

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A web-based integrative transcriptome analysis, RNAseqChef, uncovers the cell/tissue type-dependent action of sulforaphane.基于网络的综合转录组分析 RNAseqChef 揭示了萝卜硫素的细胞/组织类型依赖性作用。
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Principles and dynamics of spindle assembly checkpoint signalling.
纺锤体组装检验点信号转导的原理与动力学。
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Increased Aurora B expression reduces substrate phosphorylation and induces chromosomal instability.Aurora B表达增加会降低底物磷酸化并诱导染色体不稳定。
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Cell cycle-dependent binding between Cyclin B1 and Cdk1 revealed by time-resolved fluorescence correlation spectroscopy.通过时间分辨荧光相关光谱学揭示细胞周期依赖性细胞周期蛋白 B1 和 Cdk1 之间的结合。
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