Analysis of role of mitotic regulation and its abnormalities in carcinogenesis

G2/M期进程的异常调节导致细胞表型的剧烈变化和基因组的不稳定性。G2/M进程受两个生化事件控制，即蛋白质降解和蛋白质磷酸化。因此，这两个生化事件的调节因子被认为在肿瘤的发生发展中起着关键作用。我们项目的具体目的是：1)分析G2/M期转变的分子机制；2)阐明有丝分裂分子的异常调控作用；3)确定癌症治疗的靶点。因此，我们可以阐明Aurora-A、WARTS、CDH1和MKLP2等有丝分裂调控分子的新功能，并进一步阐明常规化疗药物诱导有丝分裂突变的分子机制。

Abnormal regulation of G2/M progression induces the drastic phenotypic changes and the genomic instability in cells. The G2/M progression is controlled by two biochemical events, protein degradation and protein phosphorylation. Therefore, regulatory factors of these two biochemical events are considered to play a critical role in development and progression of tumors. Specific aims of our project were i) to analyze molecular mechanisms regulating the transition of G2/M phase, ii) to clarify the role of abnormal regulation of the mitotic molecules and iii) to identify the targets for cancer therapies. As the results, we could elucidate the novel functions of mitotic regulating molecules including Aurora-A, WARTS, Cdh1 and Mklp2 and, furthermore, clarify the molecular mechanism of mitotic catastrophe induced by conventional chemotherapeutic agents.