细胞周期调控是目前生命科学领域的重要研究方向，其调控紊乱与基因组不稳定、肿瘤发生发展密切相关。本实验室前期研究发现，CUEDC2作为新的有丝分裂调控子，可促进基因组不稳定及肿瘤的发生（Nat.Cell Biol., 2011，共同第一作者）。近期我们通过siRNA 文库筛选发现，炎症相关蛋白TOLLIP调控有丝分裂进程，敲低TOLLIP导致染色体排列错误；深入研究发现，敲低TOLLIP引起微管着丝粒连接不稳定及纺锤体检查点异常激活。在此基础上，本项目拟通过免疫亲和纯化和质谱技术鉴定有丝分裂期与TOLLIP相互作用蛋白质，并结合免疫荧光、核型分析等技术，揭示TOLLIP调控有丝分裂期的具体分子机制，并从动物水平（炎性肿瘤模型）和临床水平阐明TOLLIP对肿瘤发生的影响。以上研究将可能发现一种炎症诱导肿瘤发生的新机制，为肿瘤生物学研究提供理论基础。

Cell cycle regulation has been an important research field in life science, whose dysregulation is closely related to genomic instability and tumorigenesis. In previous study, we found CUEDC2, as a new mitotic regulator, could promote genomic instability and tumorigenesis (Nature Cell Biology, co-first author, 2011). Here, using siRNA high-throughput screening platform, we found a inflammation-related molecules, TOLLIP (Toll-interacting Protein), specially involved in the mitotic progression, knocking down TOLLIP induced mitotic arrest and chromosome missegregation; further, we found that depletion of TOLLIP led to the unstable kinetochore-microtubule attachment and aberrant activation of spindle checkpoint. Based on these findings, we next plan to identify the interaction protein of TOLLIP in M phase by immunoaffinity purification assay and mass spectrometry, and combine usage of immunofluorescence and karyotyping method, to further study the regulatory mechanism of TOLLIP in mitosis. Our aim is to elucidate the impact of TOLLIP on tumorigenesis in the cellular, animal (inflammatory tumor model) and clinical level. Through all the study above, we might find a new mechanism of tumorigenesis induced by inflammation, and provide a fundamental basis for the research in cancer biology.