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SUMOGROUP Report Summary

Project ID: 339176
Funded under: FP7-IDEAS-ERC
Country: Germany

Periodic Report Summary 2 - SUMOGROUP (Principles of Protein Group Modification by the SUMO Pathway)

Our laboratory is specialized in studying the function of post-translational protein modification by ubiquitin family proteins. Ubiquitylation is typically a highly selective pathway in which a plethora of dedicated enzymes target individual proteins. The function of ubiquitylation is well understood and has often been studied by deletion of individual modifying enzymes or mutation of target lysines. The function of the ubiquitin-like modifier SUMO is less understood. Although SUMOylation targets roughly as many proteins as ubiquitylation, only a very small set of enzymes is responsible for protein modification in the SUMO pathway. Moreover, despite the fact that SUMO is essential, inhibiting SUMOylation of individual substrates usually does not cause deleterious phenotypes. We were able to solve this puzzle by showing that SUMOylation often targets functionally linked protein groups, where SUMO modification of the several individual subunits has additive effects and functions as intermolecular glue that stabilizes protein complexes.
Initially, we found protein group SUMOylation to be important for the formation of protein assemblies that function in homologous recombination and nucleotide excision repair. We were able to expand this concept by studying additional SUMOylated groups with relevance for cellular regulation and of medical importance. We identified the substrate repertoire of all known SUMO pathway enzymes, studied the specificity of SUMO ligases and are developing novel tools to study protein group modification. Moreover we analyzed the downstream effects of SUMOylation with a special focus on pathways that act in the disassembly of modified protein complexes.
During the first half of the funding period, we have thus made tremendous progress in gaining insights into the broad spectrum of processes involving SUMOylation. We obtained a comprehensive dataset of the yeast SUMOylome and the enzymes involved in modification of most substrate proteins. We found numerous, also previously unrecognized targets of SUMOylation, some of which we now analyze in more detail. To this end we developed novel tools to study and alter the SUMOylation of individual protein groups.
Overall, our findings are in strong support of the SUMO group model and of SUMO functioning as a stabilizer of protein complexes. However, we also found examples of different modes of action, which help us to sharpen our view of cellular control by SUMO. We studied several examples where SUMOylation inhibits complex formation or even promotes complex disassembly. Moreover, for the first time we also find a broad involvement of SUMOylation in protein quality control, demonstrating that SUMO has an important function in general proteostasis. We have also identified several modes of action for downstream effectors of SUMOylation. This includes novel targeting mechanisms for disassembly or degradation of SUMOylated protein groups, as well as additional post-translational modifications, altering the function of a SUMOylated target. In summary, we have obtained a broad view on how SUMOylation affects proteins and regulates cellular processes. Our work thus not only confirmed the SUMO group hypothesis, but also unraveled novel concepts for cellular control by the still enigmatic SUMO pathway.


Anne Katrin Werenskiold, (European Advisor)
Tel.: +49 89 8578 2601
Fax: +49 89 8578 3174
Record Number: 196880 / Last updated on: 2017-04-12
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