IDENTIFYING INHIBITORS OF THE APC/C USING YEAST MUTANTS

描述：(申请人描述) 这项研究的长期目标是使用酵母的突变体 酿酒酵母作为一种灵敏的检测系统 抗癌药物。紫杉醇、长春新碱和长春新碱等药物 对某些类型的肿瘤有效，并具有增加的光谱 在联合治疗中使用时的效率。这些药物有一个共同的靶点 它们结合微管蛋白并抑制微管功能。在没有的情况下 微管功能，细胞在细胞周期的控制下停滞 主轴检查点。检查站的最终目标是 后期促进复合体或APC/C。APC/C的大多数组件是 从酵母菌保存到人类。我建议使用温度敏感型APC/C 突变体，APC/C功能减弱，以筛选导致 变种人要死了。将使用遗传分析和表型表征 以表明这些化合物影响APC/C。从 这些研究将用于未来合理的药物设计，以合成 在酵母和哺乳动物中抑制功能齐全的APC/C的化合物 细胞。

DESCRIPTION: (Applicant's Description) The long term goals of this research is to use mutants of the yeast Saccharomyces cerevesiae as a sensitive detection system to deve1op anti-cancer drugs. Drugs such as taxo1, vinb1astine and vincristine are effective against certain type of tumors and have an increased spectrum of efficiency when used in combination therapy. The drugs have a common target in that they bind tubulin and inhibit microtubu1e function. In the absence of microtubule function, cells arrest in the cell cycle under the control of the spindle checkpoint. The ultimate target of the checkpoint is the anaphase-promoting complex or the APC/C. Most components of the APC/C are conserved from yeast to humans. I propose to use temperature sensitive APC/C mutants, enfeebled for APC/C function to screen for compounds that cause the mutants to die. Genetic analysis and phenotypic characterization will be used to show that the compounds affect the APC/C. The information gained from these studies will be used in future rational drug design to synthesize compounds that inhibit a fu1ly functional APC/C in both yeast and mammalian cells.