Highlighted Paper: A quantitative model for ordered Cdk substrate dephosphorylation during mitotic exit.

The Chromosome Segregation Laboratory, headed by Frank Uhlmann published the following paper in Cell.

Bouchoux C, Uhlmann F. A Quantitative Model for Ordered Cdk Substrate Dephosphorylation during Mitotic Exit. Cell. 2011 Nov 11;147(4):803-14.(Abstract)

Mitosis encompasses an intricately ordered series of events. Once chromosomes split in anaphase, they are first pulled to opposite cell poles by the elongating mitotic spindle. The spindle subsequently disassembles again, before finally newborn daughter cells are pinched off by cytokinesis. All these sequential mitotic events are controlled by downregulation of cyclin-dependent kinases (Cdks) and activation of a counteracting phosphatase. The correct order of mitotic events is crucial, but how ordering is achieved is poorly understood.

Using budding yeast as our model, we find that sequential mitotic events are accompanied by sequential dephosphorylation of corresponding sets of phospho-proteins. We explore a number of possibilities how dephosphorylation ordering might be achieved and show that the changing ratio of Cdk to phosphatase activity is read out by each substrate. Differences in the catalytic efficiencies of the phosphatase delineate the dephosphorylation timing of each substrate. This provides an example and an explanation for a quantitative model of cell cycle control.

Figure Legend:

Many substrates are phosphorylated by cyclin dependent kinase (Cdk) and dephosphorylated by its counteracting phosphatase Cdc14. A mechanism underlying the temporal order of sequential substrate dephosphorylation reactions is now proposed.