NKAP参与肿瘤细胞有丝分裂纺锤体检查点调控的分子机制研究

The abnormal control of mitosis is closely related with initiation and development of cancer. That is one of the most important issues in the front area of life science nowadays. Our prior research demonstrated that phosphorylated CUEDC2 have an important role in promotion of SAC (spindle assembly checkpoint) pre-inactivation，as well as induce chromosome instability and tumorigenesis (Nature cell biology，2011，co-first author).In recent work， we found another protein-NKAP (NFκB-activating protein) can also take part in the SAC regulation ，based on the RNAi screen method. The protein level of NKAP is elevated in mitosis. The tumor cells can be arrested at prometaphase, and some cells have multi-lobed nuclei when deletion of NKAP. NKAP localized at the centrosomes during mitosis, and interact with Aurora A kinase. This project will deeply demonstrate the regulatory mechanism of NKAP involved in mitotic SAC regulation,which is based on the former important clue .The main approach is applying Time-Lapse technology to real-time monitor mitosis procedure in detail,togther with cell cycle analysis ,Western blot and other methods. All the above efforts are expected to uncover the function of NKAP in tumor occurrence and development.

细胞周期调控异常与肿瘤的发生、发展密切相关，是当今生命科学前沿领域的重要问题。我们前期工作发现磷酸化的CUEDC2蛋白可促进纺锤体检查点提前灭活，并导致染色体不稳定性从而促进肿瘤发生(Nature cell biology，2011，共同第一作者)。在近期工作中，基于RNAi文库筛选，我们发现了一个新的纺锤体检查点调控蛋白质NKAP(NFκB-activating protein)，其蛋白表达量在有丝分裂期增加，且敲低其表达可导致有丝分裂前中期阻滞，部分细胞产生多核。NKAP定位于有丝分裂期的中心体，并与Aurora A激酶相互作用。本项目拟在前期已取得重要线索基础上，通过Time-Lapse技术实时监控细胞有丝分裂期进程，结合周期分析、蛋白检测等手段，深入阐明NKAP在细胞有丝分裂纺锤体检查点中的调控模式，揭示其在肿瘤发生发展中的重要功能。

细胞周期调控异常与肿瘤的发生、发展密切相关，是当今生命科学前沿领域的重要问题。我们前期工作发现磷酸化的CUEDC2蛋白可促进纺锤体检查点提前灭活，并导致染色体不稳定性从而促进肿瘤发生(Nature cell biology，2011，共同第一作者)。在近期工作中，基于RNAi文库筛选，我们发现了一个新的纺锤体检查点调控蛋白质NKAP(NFκB-activating protein)，其蛋白表达量在有丝分裂期增加，且敲低其表达可导致有丝分裂前中期阻滞，部分细胞产生多核。NKAP定位于有丝分裂期的中心体，并与Aurora A激酶相互作用。本项目拟在前期已取得重要线索基础上，通过Time-Lapse技术实时监控细胞有丝分裂期进程，结合周期分析、蛋白检测等手段，深入阐明NKAP在细胞有丝分裂纺锤体检查点中的调控模式，揭示其在肿瘤发生发展中的重要功能。