CONTROL OF MICROTUBULE DYNAMICS DURING CELL CYCLE

细胞周期中微管动力学的控制

• 批准号: 2712751
• 负责人: BIN-BING ZHOU
• 金额: $ 0.63万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2712751
• 关键词: Xenopus oocyte; cell cycle; cell growth regulation; microtubules; mitotic spindle apparatus; video microscopy

Microtubule dynamics change dramatically during the cell cycle, from the relatively stable interphase microtubules to the very dynamic mitotic spindle. Studies with cell-free extracts of Xenopus eggs have shown that the interphase-mitosis transition of microtubule dynamics involves regulation of catastrophe rate, which is induced by phosphorylation reactions mediated by cdc2 kinase. However, both catastrophe factors and substrate proteins for these kinases that may play key roles in the change of microtubule dynamics remain to be identified. To quantitate the catastrophe activities and purify the potential catastrophe factors, I have developed a simple pulsed-chase assay to measure the catastrophe rate. Using this assay, I have shown that the catastrophe factors are active in both mitotic and interphase extracts, but the activities seem modulated during the cell cycle. The objective of this proposal is to purify the catastrophe factors, study the roles of such factors in the regulation of microtuble dynamics and spindle morphogenesis. To characterize the microtubule dynamics, both biochemical assay and real time video microscopy will be used. Since microtubule plays vital role in the cell cycle regulation, therefore regulation of proliferation, this project is directly related to cancer research.

在细胞周期中，微管动力学发生了巨大的变化，从 相对稳定的间期微管到非常动态的有丝分裂 纺锤形。对非洲爪哇卵的无细胞提取物的研究表明， 微管动力学的间期-有丝分裂转变包括 由磷酸化诱导的灾变率的调节 由cdc2激酶介导的反应。然而，无论是灾难因素还是 这些激酶的底物蛋白可能在变化中起关键作用 对微管动力学的研究还有待进一步研究。为了量化 巨灾活动和净化潜在的巨灾因素，即 已经开发出一种简单的脉冲追逐分析来测量灾难 费率。使用这个分析，我已经证明了灾难因素是 在有丝分裂和间期提取液中都很活跃，但其活性似乎 在细胞周期中被调节。这项建议的目的是 提纯巨灾因素，研究巨灾因素在经济发展中的作用 微管动力学和纺锤体形态发生的调控。至 描述微管的动力学，包括生化分析和真实的 将使用时间视频显微镜。由于微管在体内起着至关重要的作用 细胞周期调节，因此调节增殖，这 该项目与癌症研究直接相关。