ISOLATION AND CHARACTERIZATION OF CELL CYCLE CHECKPOINT PROTEINS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 有丝分裂纺锤体组装检查点（SAC）是有丝分裂中唯一已知的检查点。 SAC由复杂的多信号转导通路组成，其促进细胞分裂期间染色体的适当分离。 因此，SAC的缺陷导致染色体不稳定性（CIN），这是癌症的标志。 临床上重要的是，由有丝分裂灾难引起的细胞凋亡依赖于SAC的激活。 然而，我们对SAC信号传导的了解还远未完成，SAC激活和诱导有丝分裂凋亡之间的功能性串扰也知之甚少。 这使得难以解释癌细胞对抗有丝分裂药物（例如紫杉醇）的反应或变得难治的机制，所述抗有丝分裂药物诱导纺锤体损伤或有丝分裂灾难。 因此，理解SAC（i）控制适当的染色体分离以维持细胞分裂期间的染色体稳定性和（ii）在有丝分裂中对抗有丝分裂癌症治疗药物诱导凋亡反应的分子机制是非常重要的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The mitotic spindle assembly checkpoint (SAC) is the only known checkpoint in mitosis. The SAC is composed of complex multi-signal transduction pathways that promote the proper segregation of chromosomes during cell division. As such, defects in the SAC result in chromosome instability (CIN), a hallmark of cancer. Of clinical importance, apoptosis caused by mitotic catastrophe depends on the activation of SAC. However, our knowledge of SAC signaling is far from complete, and the functional cross-talk between SAC activation and the induction of mitotic apoptosis is poorly understood. This makes it difficult to explain the mechanism by which cancer cells respond or become refractory to anti-mitotic drugs, e.g. taxol, that induced spindle-damage or mitotic catastrophe. Therefore, it is highly important to understand both the molecular mechanism by which SAC (i) controls proper chromosome segregation to maintain chromosome stability during cell division and (ii) elicits an apoptotic response in mitosis to anti-mitotic cancer therapeutic drugs.