Seminar

Reversible ubiquitylation and the control of cell signaling

Prof. Michael Clague

Professor Michael Clague is part of the Oncology, Membrane Traffic and Signaling grouping in the Physiological Laboratory. Their research is funded by CRUK, Wellcome Trust, European Union Framework 7 and North West Cancer Research Fund. * Their over-arching interest lies in the reciprocal relationship between regulation of endocytic membrane traffic and signal transduction mechanisms. They have a long-standing interest in the links between phosphoinositide metabolism and membrane traffic. More recently they have begun to explore the role of ubiquitin in regulating the properties of endosomes and the stability of selected oncogenes. * They have a specific focus on de-ubiquitinating enzymes (DUBs). Their laboratory provided the first example of specificity to a particular type of ubiquitin chain linkage (K63, AMSH) and has provided detailed characterisation of two endosomal DUBs, which regulate down-regulation of receptor tyrosine kinases (RTKs). Currently they have projects to identify DUBs germane to cancer, which may represent attractive drug targets. * They have a particular interest in the RTK, Met, which is the receptor for hepatocyte growth/scatter factor. They are interested in how an HGF-specific signaling network is generated and how this might be disregulated in cancer. Increasingly, they are turning towards large-scale proteomics based approaches. * With regard to phosphoinositide metabolism, their current focus is on the Myotubularin family of PtdIns 3-phosphatases, some of which are mutated in heritable diseases. For example mutations in MTM1 lead to Myotubular Myopathy a form of muscular dystrophy, whilst mutations in MTMR2 lead to a neuropathological condition known as Charcot-Marie-Tooth syndrome. Their laboratory played a key role in establishing the substrate specificity of this family of enzymes.