Regulation of Mps1, a protein kinase required for the spindle assembly checkpoint.

Mps1 的调节，一种纺锤体组装检查点所需的蛋白激酶。

• 批准号: G120/1030/2
• 负责人: Patrick Eyers
• 金额: $ 12.78万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G120%2F1030%2F2
• 关键词: Regulation; Mps1; protein; kinase; required

When cells divide, the genome must be copied prior to its equal partitioning to two new cells. Errors that occur during DNA segregation are passed on to progeny cells, and an absence or excess of certain gene products leads to serious diseases, such as cancer. To prevent unequal DNA distribution, cells have evolved a checkpoint mechanism in which enzymes called protein kinases monitor the arrangement and alignment of DNA in the cell, and inhibit DNA separation until all the chromosomes have been accounted for and aligned at the spindle. The protein kinase Mps1 has an important, but undefined, role in the checkpoint of all mammalian cells. Mps1 activity can be turned on or off by an unknown regulatory circuit in the cell. This study aims to identify how Mps1 activity is regulated. Several components of the checkpoint are implicated in cancer, and so molecules that directly target these proteins hold enormous promise as anti-cancer agents. A focused biochemical approach, using model cellular systems, is urgently required to facilitate an analysis of this poorly characterised checkpoint component. Importantly, these studies will generate experimental tools to investigate Mps1 function in normal cell division and in cancer cells.

当细胞分裂时，基因组必须在其均等分配给两个新细胞之前被复制。DNA分离过程中发生的错误会传递给后代细胞，某些基因产物的缺失或过量会导致严重的疾病，如癌症。为了防止DNA分布不均，细胞已经进化出一种检查点机制，其中称为蛋白激酶的酶监测细胞中DNA的排列和对齐，并抑制DNA分离，直到所有染色体都在纺锤体上排列和对齐。蛋白激酶Mps1在所有哺乳动物细胞的检查点中具有重要但未定义的作用。Mps1的活性可以通过细胞中未知的调节回路来开启或关闭。本研究旨在确定Mps1活性是如何调节的。检查点的几个成分与癌症有关，因此直接靶向这些蛋白质的分子作为抗癌剂具有巨大的前景。一个集中的生化方法，使用模型细胞系统，是迫切需要的，以促进分析这一特点不佳的检查点组件。重要的是，这些研究将产生实验工具来研究Mps1在正常细胞分裂和癌细胞中的功能。