Research Seminar: Dialogue between protein phosphatases controls progression through mitosis.

Professor Iain Hagan, Cancer Research UK Manchester Institute, University of Manchester

Wednesday 20th May, 4.00 p.m., Stacey Lecture Theatre 1

Like many pathways that change cell fate, the mitotic cell division cycle is driven by a successive series of phosphorylation events that are driven by the sequential activation of a number of protein kinases. The gain or loss of CDK-cyclin kinase activities at each rate limiting step of the cycle gates the activation of downstream kinases to promote the phosphorylation cascades that drive the duplication and segregation of chromosomes. Despite this clear and prominent role for phosphorylation in cell cycle control and the identification and characterisation of over 20 cell cycle kinases, very little is known about the modulation of the phosphatase activities that are just as important as the kinases in regulating cell cycle progression. Without these phosphatases, there could be no cyclical gain and loss of phosphate on key targets and the cell cycle would rapidly stall. This seminar will describe how a coupling between the activities of Protein Phosphatase 1 (PP1) and Protein Phosphatase 2A, that account for over 90% of cellular serine/threonine directed phosphatase activity, provides the sequential delivery of phosphatase activities to drive cells through mitosis in fission yeast. Exploratory experimentation and sequence conservation between critical regions of these phosphatases indicate that the phosphatase relay we find in yeast is highly likely to be conserved throughout eukaryotes and function in a range of signalling contexts beyond the cell cycle.