ISOLATION AND CHARACTERIZATION OF CELL CYCLE CHECKPOINT PROTEINS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 有丝分裂纺锤体组装检查点(SAC)是唯一已知的有丝分裂检查点。SAC由复杂的多种信号转导途径组成，这些信号转导途径促进了细胞分裂过程中染色体的适当分离。因此，SAC的缺陷会导致染色体不稳定(CIN)，这是癌症的一个标志。临床上重要的是，有丝分裂突变引起的细胞凋亡依赖于SAC的激活。然而，我们对SAC信号的了解还远远不够，SAC激活和诱导有丝分裂细胞凋亡之间的功能相互作用也知之甚少。这使得很难解释癌细胞对导致纺锤体损伤或有丝分裂灾难的抗有丝分裂药物(如紫杉醇)的反应或耐药的机制。因此，了解SAC(I)在细胞分裂过程中控制适当的染色体分离以维持染色体稳定的分子机制和(II)在有丝分裂过程中对抗有丝分裂癌症治疗药物引起的凋亡反应都是非常重要的。

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.