ASPP1和ASPP2 是两个在多种肿瘤中都显著下调的肿瘤抑制基因。目前已知ASPP1/2 的主要作用是激活p53 的促凋亡功能，但多项研究表明ASPP1/2具有不依赖于p53 的抑制肿瘤作用。我们通过亲和纯化得到了细胞内源ASPP1/2蛋白复合体，发现ASPP1/2可以和多个动粒相关蛋白（如Ndc80、 KNL-1 和CENP-F 等）相互作用，并且干扰ASPP1/2的表达可造成肝癌细胞有丝分裂期纺锤体装配检验点持续激活、动粒-微管的连接和染色体的分离过程出现障碍。我们还发现ASPP1/2作为一个接头蛋白，能在有丝分裂中期促进磷酸酯酶PP1对这些动粒蛋白的去磷酸化。本项研究将探讨ASPP1/2在肿瘤中下调导致染色体不稳定性的具体分子机制，和在肿瘤发生发展过程中的重要意义。

ASPP1 and ASPP2 are two tumor suppressors which are significantly downregulated in various tumors. The well-known function ASPP1/2 is to stimulate p53 pro-apoptotic function. However, many studies also indicated that ASPP1/2 can exert tumor suppression function independent of p53. We successfully isolated endogenous ASPP1/2 protein complex by two-step affinity purification. Unexpectedly, we found many kinetochore proteins such as Ndc80、KNL-1 and CENP-F existed in ASPP1/2 complex. ASPP1/2 knockdown in HCC cells impaired the kinetochore-tubulin connection and chromosome segregation, caused persistent spindle assembly checkpoint activation. One possible explanation is that ASPP1/2 promote phosphatase PP1-mediated dephosphorylation of kinetochore proteins. The aim of this project is to investigate the molecular mechanism and clinic impact of chromosomal instability caused by ASPP1/2 downregulation in tumors.