SUMO特异性蛋白酶3（SENP3）在细胞M期发生磷酸化修饰，其突变导致细胞分裂异常。但SENP3作用的分子机制及与肿瘤的关系尚未了解。我们认为SENP3整合了细胞周期调控信号，通过其磷酸化修饰与活性的改变，调控了一些关键蛋白的SUMO化修饰及其功能，从而调控细胞的分裂与染色体的稳定。SENP3的这种调控机制异常，导致细胞染色体的不稳定，从而促进肿瘤的发生发展。基于此，拟申请的课题将研究如下科学问题：1. 确定与细胞分裂有关的SENP3磷酸化位点及磷酸化修饰酶类； 2. 明确SENP3在调控细胞分裂过程中的关键SUMO化靶蛋白；3. SENP3调控细胞分裂的分子基础；4. SENP3磷酸化位点突变与肿瘤发生发展的关系。对这些问题的回答，将使我们在了解SENP3调控细胞分裂及染色体稳定的分子机制的基础上，进一步认识与理解SENP3在肿瘤发生发展中的作用和意义.

In preliminary study, we found that SENP3 was highly phosphorylated in Mitosis. The mutation of phosphorylation site affected SENP3 activity and caused aneupoidy and chromosome instability.Thus, we propose that cell cycle signals stimulate SENP3 phosphorylation,which is essential for the regulation of SUMOylation of key proteins in mitosis and then prevents chromosome mis-segregation.As chromosome instability is a hallmark of tumor cell,the mutation of phosphorylation site of SENP3 will promote the tumnorigenesis. In this study, we will aim at: 1.to determine which phosphorylation sites of SENP3 are related to the regulation of cell mitosis, and which kinase and phosphatase control SENP3 phosphorylation in mitosis; 2. to determine the target of SENP3 de-SUMOylation in mitosis; 3. to investigate the molecular basis underlying the mitosis regulation of SENP3;4. to determine the role of the mutation of SENP3 phosphorylation sites in tumorigenesis.these proposed studies will advance our understanding of the role of SENP3 in the regulation of mitosis and tumorigenesis.