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

点击翻译按钮获取中文摘要

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.