Kinesin-regulated microtubule dynamics

描述（由申请人提供）：动态微管聚合物是成功细胞分裂所必需的。由于微管在有丝分裂中的核心作用，抑制微管动力学的药物可以有效地破坏细胞分裂，通常被用作抗癌药物。体内辅助蛋白紧密调节微管动力学。促进微管转换的蛋白的异常高表达与对微管毒物治疗产生抗性的侵袭性肿瘤相关。专注于了解这些辅助蛋白功能的详细研究可能会为新的化疗策略铺平道路。该研究旨在精确定义三种相关的运动蛋白样运动蛋白如何影响微管动力学，以促进人类细胞中有丝分裂染色体的适当分离。灵敏试验将被用来直接测量这些驱动蛋白的机械化学性质和细胞功能。这项工作的目标是充分了解激酶-8蛋白如何在其他微管动力学调节剂的背景下发挥作用，以确保成功的细胞分裂。明确微管细胞骨架调控因子之间的功能关系将为癌症生物学的研究提供新的方向。

DESCRIPTION (provided by applicant): 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.