Sir Tim Hunt
Clare Hall Laboratories, Cancer Research UK, South Mimms, Potters Bar, Hertfordshire, UK F1000 Section Head (since 18 July 2001)BIOGRAPHY
CURRENT POSITION:Tim has now closed his Lab at Clare Hall Laboratories, but remains an Emeritus Group Leader.
EDUCATION:
• BA University of Cambridge (1964)
• PhD University of Cambridge (Biochemistry) 1968
HONORS AND AWARDS:
• Fellow of the Royal Society
• Foreign Member of the US National Academy of Sciences
• Nobel Prize, Physiology or Medicine, 2001
RESEARCH INTERESTS:
I'm currently most interested in the control of mitosis; why cells don't enter mitosis until they have completed S-phase, and how they get out of mitosis. Research interests are presently focussed on the protein phosphatases that dephosphorylate mitotic phosphoproteins. But we recently identified a particular form of PP2A that seems to be crucial for the control of the relative activity of Wee1 and Cdc25. These enzymes are controlled by PP2A-B55, which in its active form turns on Wee1 and turns Cdc25 off, resulting in inactive CDK1. As cyclins accumulate, however, a small amount of CDK1 activity appears, which gradually turns off PP2A-B55 by a novel mechanism involving a protein kinase called greatwall and two substrates of greatwall, ARPP-19 and Edosulfine, which bind to and inhibit PP2A-B55 when they are phosphorylated. This in turn allows phosphorylation of Wee1 and Cdc25, which turn off and on respectively, allowing CDK1 to express its full activity and modify hundreds of proteins in the cell. Somehow, the degradation of cyclin by polyubiquitylation (catalysed by the APC/C) allows the whole system to revert to its interphase form, and protein phosphatases are activated to catalyse the return to interphase. The control of the APC/C by multisite phosphorylation is not very well understood.
HOME PAGE
http://www.london-research-institute.org.uk/research/past-researchers/tim-hunt
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