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Protein Kinase Regulation by the HSP90 Molecular Chaperone System

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This talk will take place online via Zoom & Kings Hedges Room

Abstract: The HSP90 molecular chaperone, in collaboration with its co-chaperone CDC37 plays a critical role in the cellular stabilisation, activation and regulation of a substantial proportion of the kinome, including most of the protein kinases that drive development and progression of cancer. Work from our lab and others over several decades has revealed some of the mechanisms by which HSP90 -CDC37 engages with its protein kinase clients, how this affects their structure and activity, and how drugs targeted at HSP90 and its kinase clients can modulate this. In this talk I will summarise what we know about HSP90 -CDC37 interactions with protein kinases, discuss the discovery and characterisation of a novel E3 ubiquitin ligase that mediates kinase degradation when HSP90 function is impaired, and present new results that show how HSP90 -CDC37 facilitates comprehensive dephosphorylation and ‘factory reset’ of client protein kinases by the protein phosphatase PP5 .

Biography: Laurence Pearl is Professor of Structural Biology in the Genome Damage and Stability Centre at the University of Sussex, where he was Head of the School of Life Sciences from 2009 to 2017, and is also Head of the Division of Structural Biology at The Institute of Cancer Research in London. His laboratory studies the structural biology of the DNA Damage Response and the HSP90 molecular chaperone system, and seeks to translate these basic studies for the development of new drugs for the treatment of cancer and other diseases. He is a Fellow of the Royal Society (FRS), a Fellow of the Academy of Medical Sciences (FMedSci) and an elected member of the European Molecular Biology Organisation (EMBO) and the Academia Europeae. In 2013 he shared the CR-UK Translational Cancer Research Prize (with Paul Workman, ICR ) for uncovering HSP90 as a novel target in cancer therapy and for the development of the leading HSP90 inhibitor, AUY922 . He was awarded the 2018 Novartis Medal and Prize by the Biochemical Society.

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