Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, Korea.
Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul, 02447, Korea.
Cell Death Dis. 2022 Jun 7;13(6):534. doi: 10.1038/s41419-022-04990-8.
CCAR2 (cell cycle and apoptosis regulator 2) is a multifaceted protein involved in cell survival and death following cytotoxic stress. However, little is known about the physiological functions of CCAR2 in regulating cell proliferation in the absence of external stimuli. The present study shows that CCAR2-deficient cells possess multilobulated nuclei, suggesting a defect in cell division. In particular, the duration of mitotic phase was perturbed. This disturbance of mitotic progression resulted from premature loss of cohesion with the centromere, and inactivation of the spindle assembly checkpoint during prometaphase and metaphase. It resulted in the formation of lagging chromosomes during anaphase, leading ultimately to the activation of the abscission checkpoint to halt cytokinesis. The CCAR2-dependent mitotic progression was related to spatiotemporal regulation of active Aurora B. In conclusion, the results suggest that CCAR2 governs mitotic events, including proper chromosome segregation and cytokinetic division, to maintain chromosomal stability.
CCAR2(细胞周期和凋亡调节剂 2)是一种多功能蛋白,可在细胞受到细胞毒性应激后参与细胞存活和死亡。然而,关于 CCAR2 在没有外部刺激的情况下调节细胞增殖的生理功能知之甚少。本研究表明,CCAR2 缺失细胞具有多叶核,表明细胞分裂存在缺陷。特别是,有丝分裂阶段的持续时间受到干扰。这种有丝分裂进程的干扰是由于前期和中期着丝粒过早失去了与着丝粒的连接,以及纺锤体组装检查点失活所致。这导致在后期形成滞后染色体,最终激活分裂检查点以阻止胞质分裂。CCAR2 依赖性的有丝分裂进程与活跃的 Aurora B 的时空调节有关。总之,研究结果表明,CCAR2 控制有丝分裂事件,包括正确的染色体分离和胞质分裂,以维持染色体稳定性。