UCLA

The discovery of novel cell division proteins is important to further understand the basic mechanisms of cell division. Equally important is an understanding of how these proteins are misregulated to induce cell proliferation and the associated human diseases like cancer. Therefore, the discovery of novel cell division proteins and their functional characterization creates opportunities to define new cancer targets that can be used to develop new cancer therapeutics. The primary goal of this thesis was to identify new enzymes that are misregulated in cancer cells and to understand their functions during cell division. The first enzyme that I analyzed was the previously uncharacterized protein Myl5, which is a myosin regulatory light chain (RLC). I determined that Myl5 localizes to the mitotic spindle and is important for cell division. Depletion of MYL5 in cancer cells led to mitotic defects and a slower transition through mitosis. In contrast, overexpression of MYL5 in cancer cells led to a faster mitosis. To my knowledge this the first myosin RLC that has been implicated in mitotic spindle assembly. The second protein that I analyzed was the cyclin dependent kinase Cdk14. Cdk14 has been linked to the cell cycle via the WNT signaling pathway. However, Cdk14 had not been implicated in cell division. My work showed that Cdk14 localizes to the mitotic spindle during mitosis and its down regulation resulted in severe mitotic defects and a faster cell division. This study enhanced our understanding of how the spindle assembly checkpoint (SAC) is regulated and how its dysregulation can impact cancer cell proliferation and anticancer drug resistance. Together, my work on Myl5 and Cdk14 has elucidated the function of these two previously underappreciated proteins in cell division.