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