Ron Hay

Ron Hay

Talk Title: Remodeling of the SUMO proteome in response to proteotoxic stress.


Ron Hay gained a BSc in Biochemistry at Heriot-Watt University, Edinburgh (1975), a PhD in Virology from Glasgow University (1979) and was a postdoc at Harvard Medical School, Boston. Returning to the MRC Virology Unit he established his independent laboratory (1982-1985), then moved to the University of St. Andrews where he held Lecturer and Reader positions before taking up the Chair in Molecular Biology. In October 2005 he took up the Chair of Molecular Biology in the University of Dundee and is part of the Centre for Gene Regulation and Expression. Ron’s research has established conjugation with the Small Ubiquitin-like Modifier (SUMO) as an important regulatory mechanism in eukaryotes. Ron is a Wellcome Trust Senior Investigator and a fellow of the Royal Society, the Royal Society of Edinburgh, the Academy of Medical Sciences, Academia Europaea and is a member of the European Molecular Biology Organisation.


Remodeling of the SUMO proteome in response to proteotoxic stress.
Ronald T. Hay

Centre for Gene Regulation and Expression, University of Dundee, UK
Many cancer treatments rely on the induction of proteotoxic stress for therapeutic activity. Arsenic trioxide, bortezomib (proteasome inhibitor) and heat stress are all used to treat different cancers and are also know to trigger changes in modification of proteins by the small ubiquitin-like modifiers (SUMOs). We developed a specific peptide enrichment strategy that enables the identification of SUMO acceptor lysine residues on a proteome-wide scale. Conjugation to substrates of a SUMO-2 variant with Threonine 90 mutated to Lysine produces a Gly-Gly remnant on target lysines after cleavage with endoproteinase Lys-C. This allows specific enrichment of SUMO-modified peptides using diglycyl-lysine antibodies. Furthermore, it leaves a diagnostic signature that cannot be confused with other modifications. This has allowed the direct identification of over 6000 target lysines in 2000 human proteins in response to heat stress. These data help us to build models to explain the substrate specificity of SUMO modification