KINASE REGULATION DURING THE METAPHASE-ANAPHASE TRANSITION IN MITOSIS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 忠实的染色体分离依赖于细胞机制，监测微管-动粒附着。正确的附着允许细胞进入下一个细胞周期，而错误会导致细胞周期停滞，直到它们被纠正。触发这种停滞的信号要么是动粒和微管之间缺乏附着，要么是纺锤体缺乏张力。 已知这种信号传导涉及纺锤体检查点蛋白和其他有丝分裂激酶和磷酸酶。 然而，这些组分如何协调地调节细胞周期尚未完全了解，部分原因是许多有丝分裂激酶在整个细胞周期中发挥多种功能。为了解决这个问题，我们正在进行亲和纯化和质谱分析的有丝分裂激酶复合物从不同的细胞周期阶段，并在不同状态的微管-动粒附着，以确定蛋白质-蛋白质相互作用和翻译后修饰的任何差异。 这将使我们能够了解这些复合物是如何调节响应错误的微管动粒附件。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Faithful chromosome segregation relies on the cellular mechanism that monitors microtubule-kinetochore attachment. The correct attachment allows cells to progress to the next cell cycle, while errors cause cell cycle arrest until they become corrected. The signal to trigger this arrest is either lack of attachment between kinetochore and microtubule or lack of tension in the spindle. This signaling is known to involve spindle checkpoint proteins and other mitotic kinases and phosphatases. However, how these components function coordinately to regulate the cell cycle has not been fully understood, partly because many mitotic kinases conduct multiple functions throughout the cell cycle. To address this issue, we are conducting affinity purification and mass spectrometric analysis of mitotic kinase complexes from different cells cycle stages and in different states of microtubule-kinetochore attachment to identify any differences in protein-protein interactions and post-translational modifications. This will allow us to understand how these complexes are regulated in response to errors in microtubule-kinetochore attachment.