在有丝分裂过程中，母代遗传信息通过均等的染色体分离精确地传递给子代细胞。染色体分离的失调会导致非整倍体和染色体不稳定性，危害个体发育与健康。纺锤体检验点是保证精准的染色体分离的首要机制，阐明它的调控机制对于促进人类健康具有重要意义。Mps1激酶是维持纺锤体检验点功能的关键因子，但是它在动粒定位的分子机制和它如何调控Mad2的活性仍尚未被阐明。我们拟结合工作基础，利用多学科交叉的手段研究Mps1动粒定位的调控机制，阐明Aurora B和其自身活性调控Mps1动粒定位的分子机制，解析Ndc80复合物与Mps1的相互作用，探究Mps1的动粒定位和纺锤体检验点强度之间的关联。我们也将解析Mps1如何调控Mad2的动粒定位与活性来揭示纺锤体检验点的信息流。通过本项目的实施，我们希望揭示Mps1动粒定位的分子基础和其促进Mad2活性的分子机制，为阐明染色体不稳定性与肿瘤的发生发展提供理论基础。

During mitosis, through equal chromosome segregation, mother cell faithfully transmits the genetic information into two daughter cells. The failure of faithful chromosome segregation during mitosis will generate aneuploidy daughter cells and chromosomal instability (CIN). CIN will drive aggressive tumorigenesis by allowing tumor to evolve rapidly and acquire malignant transformation ability. The spindle assembly checkpoint (SAC) is a surveillance mechanism that ensures accurate chromosome segregation during mitosis. Therefore, elaborating the molecular mechanism of SAC is of great value to promote the health of human being. Mps1 protein kinase plays essential function in SAC in different species. However, the detailed molecular basis of Mps1 kinetochore localization and how does it promote the kinetochore recruitment and activity of Mad2 remain poorly understood. In this proposal, we aim to uncover the molecular basis of kinetochore targeting of Mps1 and explore the function of Mps1 in the maintenance of SAC signaling. Using the methods of molecular biology, cell biology, biochemistry and biophotonics, we will explore the molecular basis of Mps1 kinetochore localization, address the molecular mechanism of how Aurora B and Mps1 itself promote Mps1 recruitment, dissect the complicated interaction between Ndc80 complex and Mps1 and explore and relationship between Mps1 kinetochore and SAC signaling strength. We also aim to explore how Mps1 promote Mad1/Mad2 kinetochore recruitment. Overall, we aim to discover the molecular mechanism of Mps1 kinetochore targeting and how Mps1 ensures Mad1/Mad activity when the SAC signaling in on. We hope our research will provide novel knowledge for the elucidation of chromosomal instability and tumorgenesis.