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Biozentrum Lectures 2010

Getting in and out of Mitosis: Fresh Light on Protein Phosphatases

Tim Hunt, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire
October 12, 2010, Time: 16:00, Hörsaal 1, Pharmazentrum, Klingelbergstrasse 50-70, Basel

The process of mitosis involves a reorganisation of the cell, i.e. chromosomes condense, the nuclear envelope breaks down, and the mitotic spindle is assembled. This reorganisation is triggered by the activation of a protein kinase called Cyclin-Dependent Kinase 1 (CDK1). The end of mitosis is marked by the proteolysis of the cyclin subunit of CDK1, which terminates kinase activity. At this point, the phosphate moieties that altered the properties of hundreds of proteins to bring about the cellular reorganisation are removed by protein phosphatases.It is difficultto see how proteins could be fully phosphorylated if both kinases and phosphatases were simultaneously active. Thus it is quite likely that protein phosphatases are shut off as cells enter mitosis and are reactivated when mitosis is complete, allowing return to interphase.It emerged that at least one protein phosphatase in the PP2A family was shut off in mitosis. Depletion of this particular phosphatase accelerated entry into mitosis and blocked exit from mitosis. We have discovered how this phosphatase is regulated. It entails binding a small inhibitor protein that is phosphorylated by a protein kinase called greatwall, itself a substrate of CDK1. In this Biozentrum lecture, I will explain how we found this out and discuss the role of this particular control mechanism in the control of mitosis.

Tim Hunt is a ‘Principal Scientist’ (note, not THE principal scientist) at Cancer Research UK, Clare Hall Laboratories, in South Mimms, Hertfordshire. Dr. Hunt was born in 1943 and grew up in Oxford until he was 18 years old, when he moved to Cambridge to read Natural Sciences completing his Ph.D. on “The Synthesis of Haemoglobin” in the Department of Biochemistry. He spent almost 30 years altogether in Cambridge, mostly working on the control of protein synthesis, was a postdoctoral Fellow at the Albert Einstein College of Medicine and spent many summers at the Marine Biological Laboratory, Woods Hole, both teaching and doing research. In 1982, he discovered cyclins, which turned out to be compo-nents of “Key Regulator(s) of the Cell Cycle”, and led to a share of the Nobel Prize in Physiology or Medicine in 2001, together with Lee Hartwell and Paul Nurse. Dr Hunt has helped write two books: Together with Andrew Murray, he wrote “The Cell Cycle: An Introduction” and with John Wilson composed “Molecular Biology of the Cell: The Problems Book” to accompany the textbook by Alberts et al.Apart from researching, writing and lecturing, Dr Hunt findshimself on numerous scientificadvisory panels. He chaired the Life Sciences Panel for selection of Euro-pean Young Investigators under the aegis of the European Science Foundation and was chairman of the council of EMBO. He actively promoted the idea of the European Research Council by lobbying commissioners and MEPs in Brussels. Dr Hunt is a Fellow of the Royal Society, a Fellow of the Academy of Medical Sciences, a Foreign Associate of the National Academy of Sciences of the USA, a Member of EMBO, a Foreign Member of the American Academy of Arts and Sciences and a Member of Academia Europaea. He was knighted in June 2006. He is married to Mary Collins, who is Dean of Life Sciences at University College London. They have two children, Celia (15) and Agnes (12).