Dynamic microtubule polymers are required for successful cell division. Due to the central role of microtubules in mitosis, pharmacological agents that suppress microtubule dynamics effectively disrupt cell division and are commonly used as anti-cancer drugs. Accessory proteins in vivo tightly regulate microtubule dynamics. Abnormally high expression of proteins that promote microtubule turnover is correlated with aggressive tumors that are resistant to treatment with microtubule poisons. Detailed studies focused on understanding how these accessory proteins function will likely pave the way to new chemotherapeutic strategies. The proposed study aims to precisely define how three related kinesin-like motor proteins affect microtubule dynamics to promote proper mitotic chromosome segregation in human cells. Sensitive assays will be employed to directly measure the mechanochemical properties and cellular functions of these kinesins. The goal of this work is to fully understand how kinesin-8 proteins function in the context of other modulators of microtubule dynamics to ensure successful cell division. Defining the functional relationships between regulators of the microtubule cytoskeleton will foster new directions for the study of cancer biology. ? ? ?
