Eg5作为一个微管依赖性的有丝分裂驱动蛋白，通过其ATPase活性，交联微管并使微管反向平行滑动，对于两极纺锤体的装配和纺锤体的维持均至关重要，而且与肿瘤的发生密切相关。但是，Eg5的活性、定位和功能的调控机制并不清楚。本课题将分析DAPK1与Eg5的相互作用，探讨DAPK1对Eg5的磷酸化，并鉴定被磷酸化的氨基酸残基。本课题还将研究DAPK1介导的Eg5磷酸化如何影响Eg5的ATPase活性，如何影响Eg5在纺锤体上和纺锤体两极的定位，以及如何影响Eg5对纺锤体装配和维持的调节。此外，本课题将通过开展细胞和分子生物学实验，结合动物模型及临床肿瘤样品，探讨DAPK1介导的Eg5磷酸化在胰腺癌发生发展中的作用。这些研究工作的开展能够提高对细胞分裂的分子机制的理解，并加深对胰腺癌发病机理的认识。

Eg5 is a microtubule-dependent mitotic kinesin. By crosslinking microtubules and enabling anti-parallel microtubule movement via its ATPase activity, Eg5 plays a critical role in the assembly and maintenance of the bipolar spindle and has been implicated in cancer development. However, the molecular mechanism that regulates the activity, localization, and function of Eg5 remains elusive. In this project, we will analyze the interaction between DAPK1 and Eg5, examine the phosphorylation of Eg5 by DAPK1, and identify the phosphorylated amino acid residue. We will also investigate how DAPK1-mediated Eg5 phosphorylation regulates the ATPase activity of Eg5, regulates the localization of Eg5 on the spindle and spindle poles, and regulates the role of Eg5 in spindle assembly and maintenance. In addition, we will study the role of DAPK1-mediated Eg5 phosphorylation in pancreatic cancer development and progression, by performing cellular and molecular biology experiments and using animal models and clinical cancer samples. These studies will improve our understanding of the molecular mechanisms of cell division and pancreatic cancer pathogenesis.