Controlling cell cycle progression from the spindle pole
Progression through the cell division cycle is promoted by the sequential activation of different Cdk-Cyclin kinase complexes. Cdk1-Cyclin B kinase activation drives progression through the final stage of the cycle: Mitosis. Because active Cdk1-Cyclin B will push cells into division from any stage in the cell cycle, Wee1 kinase phosphorylates Cdk1 to restrain activity until Cdc25 removes this phosphate to trigger division at the appropriate time. Our work with fission yeast indicates that events on the centrosome play a key role in promoting Cdk1-Cyclin B activity to trigger division. Simply blocking the recruitment of Protein Phosphatase 1 to a spindle pole scaffold protein enables cells to tolerate the otherwise lethal removal of Cdc25. The summation of signalling outputs from neighbouring scaffolds suggests that the centrosome assumes such a prominent role in directing cell division because it provides a single location where signals from diverse pathways can be integrated to generate a single, coherent, output that dictates the time at which a cell divides.
Professor, Cancer Research UK Manchester Institute
Domain 4 - UMR 144 - Subcellular Structure and Cellular Dynamics