有丝分裂期染色体异常分离是导致染色体不稳定性的重要机制，在肿瘤的发生发展过程中具有重要作用。最近我们研究发现PinX1对于细胞有丝分裂期染色体的正常分离至关重要，但具体分子机制尚不明确。在前期青年科学基金项目资助下，我们发现一个新的PinX1 相互作用蛋白Plk1，也证实Plk1 在体外能够磷酸化修饰PinX1，进一步研究显示Plk1 磷酸化修饰PinX1 发生在细胞有丝分裂期，且对于细胞染色体的正常分离是必须的。本课题拟在前期工作基础上，观察Plk1 磷酸化修饰PinX1 对PinX1 调控染色体分离和染色体稳定性的影响，并进一步阐明具体分子机制；同时，筛选和鉴定新的磷酸化修饰PinX1 蛋白相互作用蛋白，并评估其在调控染色体正常分离中的作用。本项目的进行不仅有助于深入了解肿瘤发生发展机制，也为临床上开发针对染色体不稳定性的抗肿瘤靶向治疗药物，提供理论基础和实验依据。

It has been evident that chromosome instability due to inaccurate chromosome　segregation in mitosis, plays a major role in the development of neoplasm. Recently, our study showed that PinX1 is essential for faithful chromosome segregation, but the exactly molecular mechanism　needs further study. Supported by previous National Natural Science Foundation of　China for the Youth, we identified a novel PinX1-binding protein, Plk1, and validated　the Plk1 can phosphorylate PinX1 in vitro. Further study showed that the　phosphorylation of PinX1 by Plk1 occurs in mitosis and is essential for faithful　chromosome segregation. Based our previous studies, our further investigation is　to study the effect of phosphorylation of PinX1 by Plk1 on accurate chromosome　segregation and chromosome　stability and clarify the exact molecular mechanism,　to identify new phosphorylated PinX1 interacting protein and evaluate its role in　regulation of faithful chromosome segregation. Our project will help to further　understand the mechanisms of tumor formation and provide experimental data to develop anti-tumor drugs aimed at chromosome instability in clinic.