Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen
Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen
复制标题
DOI：
10.1126/science.286.5441.971
复制
发表时间：
1999-10-29
期刊：
影响因子：
56.9
通讯作者：
Mitchison, TJ
中科院分区：
文献类型：
--
作者：
Mayer, TU;Kapoor, TM;Mitchison, TJ
干扰特定蛋白质功能的小分子是解剖哺乳动物细胞中复杂过程的有价值的工具。两种基于表型的筛选的组合，一种基于特定的翻译后修饰，另一种可视化微管和染色质，用于鉴定影响有丝分裂的化合物。一种化合物，在这里命名为monastrol，在有丝分裂中用单极纺锤体阻止哺乳动物细胞。在体外，monastrol特异性地抑制有丝分裂驱动蛋白Eg5的运动性，Eg5是纺锤体双极性所需的马达蛋白。所有先前已知的特异性影响有丝分裂机制的小分子靶向微管蛋白。因此Monastrol将是研究有丝分裂机制的一个特别有用的工具。
Small molecules that perturb specific protein functions are valuable tools for dissecting complex processes in mammalian cells. A combination of two phenotype-based screens, one based on a specific posttranslational modification, the other visualizing microtubules and chromatin, was used to identify compounds that affect mitosis. One compound, here named monastrol, arrested mammalian cells in mitosis with monopolar spindles. In vitro, monastrol specifically inhibited the motility of the mitotic kinesin Eg5, a motor protein required for spindle bipolarity. All previously known small molecules that specifically affect the mitotic machinery target tubulin. Monastrol will therefore be a particularly useful tool for studying mitotic mechanisms.