Kohno M, Hattori A, Yamaguchi H
Laboratory of Cell Biology, Gifu Pharmaceutical University.
Gan To Kagaku Ryoho. 1997 Jan;24(2):164-77.
Microtubules are stiff polymers that extend throughout the cytoplasm of eukaryotic cells and regulate the location of intracellular compartments. Microtubules are formed by the polymerization of tubulin molecules, each of which is a heterodimer consisting of two closely related globular polypeptides, alpha-tubulin and beta tubulin. Many of the microtubule arrays are labile and are turning over rapidly; they depolymerize and repolimerize continually in living cells. One of the most striking examples is the mitotic spindle, which forms after the cytoplasmic microtubules disassemble at the onset of mitosis. The mitotic spindle is the target of a variety of agents that act by interfering with the exchange of tubulin subunits between the microtubules and the free tubulin pool; some of these agents can be used as antimitotic or anticancer drugs. We recently have developed a simple and sensitive method of screening for tubulin inhibitors, to which we have successfully applied the nerve growth factor/PC12 cell system. In this report, we describe the details of this method for screening tubulin inhibitors, by which we have analyzed several well-known and new compounds a model experiments.
微管是一种坚硬的聚合物，贯穿于真核细胞的整个细胞质，并调节细胞内区室的位置。微管由微管蛋白分子聚合而成，每个微管蛋白分子都是一个异二聚体，由两个密切相关的球状多肽α-微管蛋白和β-微管蛋白组成。许多微管阵列不稳定，周转迅速；它们在活细胞中不断解聚和重新聚合。最显著的例子之一是有丝分裂纺锤体，它在有丝分裂开始时细胞质微管解体后形成。有丝分裂纺锤体是多种通过干扰微管与游离微管蛋白池之间微管蛋白亚基交换而起作用的药物的作用靶点；其中一些药物可用作抗有丝分裂或抗癌药物。我们最近开发了一种简单而灵敏的筛选微管蛋白抑制剂的方法，并已成功地将其应用于神经生长因子/PC12细胞系统。在本报告中，我们描述了这种筛选微管蛋白抑制剂方法的细节，通过该方法我们对几种知名和新型化合物进行了模型实验分析。
