A proteomics-based approach for the analysis of sumoylation patterns in normal and apoptotic human cells

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Sumoylation, a protein modification, is defined by the covalent and reversible attachment of the protein SUMO to the target protein. This pathway is required for mammalian cell survival, arguing for its critical role.  Only small amounts of sumoylated proteins are found modified in natural conditions, making their identification difficult. Nonetheless, dozens of cellular and viral proteins haven been shown to be modified by SUMO, and it is likely that many more remain to be identified. Although the outcome of sumoylation has been well characterized for individual proteins, the importance of sumoylation (as a pathway) in specific cellular functions is poorly understood. The proposed research program will use proteomic tools for the purification of human sumoylated proteins involved in specific pathways. SUMO targets will be identified, then we will use genetic tools to investigate the impact of sumoylation for these individual proteins. This proteomics/functional dual approach will be first applied to investigate the relationships between sumoylation and apoptosis (programmed cell death) as well as cell cycle progression. Specifically, we will identify proteins that are either sumoylated or desumoylated at various cell cycle stages and following apoptosis induction. Then we will analyze in details the role of sumoylation for these proteins. We expect that this project will identify new protein targets of SUMO and show the role of this modification in the normal and apoptotic cell. This work might also identify new targets for cancer therapies aimed at regulating the cell cycle. On the long term, we will apply this approach to investigate the importance of sumoylation in other contexts such as viral infections.