中国科学技术大学Liangyu Zhang等研究人员合作发现，PLK1磷酸化ZW10引导有丝分裂中染色体的准确分离。这一研究成果于2024年2月24日在线发表在《分子细胞生物学报》上。

研究人员发现了PLK1诱导的ZW10磷酸化调节有丝分裂中纺锤体检查点沉默的调控机制。ZW10是PLK1的同源底物，ZW10在Ser12处的磷酸化使ZW10-Zwint1能动态地相互作用。抑制ZW10的磷酸化会导致染色体错位，而持续表达磷酸化模拟ZW10突变体会导致有丝分裂后期过早，在细胞进入无丝分裂期时姐妹染色单体会纠缠在一起。

这些发现揭示了PLK1-ZW10先前未被描述的相互作用，通过这种相互作用，ZW10的动态磷酸化可对有丝分裂中染色体的准确分离进行微调。

据介绍，细胞分裂过程中遗传信息的稳定传递需要忠实的染色体分离。越来越多的证据表明，PLK1在动粒处的动态控制着正确的动粒-微管连接以及随后的纺锤体检查点沉默。然而，PLK1介导的纺锤体检查点沉默的内在机制仍然难以捉摸。

附：英文原文

Title: PLK1 phosphorylation of ZW10 guides accurate chromosome segregation in mitosis

Author: Bellah, Sm Faysal, Xiong, Fangyuan, Dou, Zhen, Yang, Fengrui, Liu, Xing, Yao, Xuebiao, Gao, Xinjiao, Zhang, Liangyu

Issue&Volume: 2024-02-24

Abstract: Stable transmission of genetic information during cell division requires faithful chromosome segregation. Mounting evidence has demonstrated that PLK1 dynamics at kinetochores control correct kinetochore–microtubule attachments and subsequent silencing of the spindle checkpoint. However, the mechanisms underlying PLK1-mediated silencing of the spindle checkpoint remain elusive. Here, we identified a regulatory mechanism by which PLK1-elicited ZW10 phosphorylation regulates spindle checkpoint silencing in mitosis. ZW10 is a cognate substrate of PLK1, and the phosphorylation of ZW10 at Ser12 enables dynamic ZW10–Zwint1 interactions. Inhibition of ZW10 phosphorylation resulted in misaligned chromosomes, while persistent expression of phospho-mimicking ZW10 mutant caused premature anaphase, in which sister chromatids entangled as cells entered anaphase. These findings reveal the previously uncharacterized PLK1–ZW10 interaction through which dynamic phosphorylation of ZW10 fine-tunes accurate chromosome segregation in mitosis.

DOI: 10.1093/jmcb/mjae008

Source: https://dx.doi.org/10.1093/jmcb/mjae008