Reference number : GC-2017-Q1-03181, amendment number : , agreement type : G, recipient legal name : Berthoux, Lionel (Université du Québec à Trois-Rivières), recipient country : CA, recipient province : nan, recipient city : Quebec|Québec, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : TRIM proteins are a large family of proteins that share a common basic structure but are very diverse in their functions and subcellular localization. They harbor a domain called the RING finger which has an &ldquo;E3 ubiquitin ligase&rdquo; activity, meaning that it guides the protein modification process known as ubiquitination. Ubiquitination consists in the linkage of a small protein, ubiquitin, to other proteins. It is believed that their ubiquitin ligase activity is central to the function of TRIM proteins. Some TRIM proteins were found to be themselves subjected to another protein modification process known as SUMOylation. SUMOylation also consists in the linkage of a small protein, SUMO, to another protein and occurs at consensus sites. SUMOylation often modulates the intracellular localization, stability and/or function of the modified proteins. Interestingly, ubiquitination and SUMOylation are inter-dependent processes. Work in our laboratory showed that one human TRIM in particular, TRIM5&alpha;, harbors a consensus SUMOylation site that modulates the ubiquitin ligase activity of the adjacent RING domain. Computer searches for SUMOylation consensus sites suggested that the majority of human TRIM proteins harbor such motifs, implying that SUMOylation plays an important and general role in the function of proteins of this family. 
We propose to establish a research program with the long-term goal of deciphering the functional relationships between TRIM proteins and SUMOylation . We will clone, express and purify all ~80 human TRIM proteins, including some that have never been studied. Their capacity to bind SUMO and to be SUMOylated will be investigated. SUMOylation will be tested in cells and using in vitro assays, and SUMOylation sites will be identified. The role of SUMOylation and SUMO-relevant motifs in the behavior of TRIM proteins will be assessed by analyzing their impact on the subcellular localization, stability and E3 ubiquitin ligase activity. This research program will yield the first detailed description of the TRIM proteins SUMOylation landscape and will uncover the role of SUMOylation in TRIM functions. Our systematic approach will allow us to uncover regulatory pathways common to multiple TRIM proteins and to characterize poorly studied members of the TRIM family. In addition to significantly advancing scientific knowledge, this research program has potential applications in protein engineering., program purpose french : TRIM proteins are a large family of proteins that share a common basic structure but are very diverse in their functions and subcellular localization. They harbor a domain called the RING finger which has an &ldquo;E3 ubiquitin ligase&rdquo; activity, meaning that it guides the protein modification process known as ubiquitination. Ubiquitination consists in the linkage of a small protein, ubiquitin, to other proteins. It is believed that their ubiquitin ligase activity is central to the function of TRIM proteins. Some TRIM proteins were found to be themselves subjected to another protein modification process known as SUMOylation. SUMOylation also consists in the linkage of a small protein, SUMO, to another protein and occurs at consensus sites. SUMOylation often modulates the intracellular localization, stability and/or function of the modified proteins. Interestingly, ubiquitination and SUMOylation are inter-dependent processes. Work in our laboratory showed that one human TRIM in particular, TRIM5&alpha;, harbors a consensus SUMOylation site that modulates the ubiquitin ligase activity of the adjacent RING domain. Computer searches for SUMOylation consensus sites suggested that the majority of human TRIM proteins harbor such motifs, implying that SUMOylation plays an important and general role in the function of proteins of this family. 
We propose to establish a research program with the long-term goal of deciphering the functional relationships between TRIM proteins and SUMOylation . We will clone, express and purify all ~80 human TRIM proteins, including some that have never been studied. Their capacity to bind SUMO and to be SUMOylated will be investigated. SUMOylation will be tested in cells and using in vitro assays, and SUMOylation sites will be identified. The role of SUMOylation and SUMO-relevant motifs in the behavior of TRIM proteins will be assessed by analyzing their impact on the subcellular localization, stability and E3 ubiquitin ligase activity. This research program will yield the first detailed description of the TRIM proteins SUMOylation landscape and will uncover the role of SUMOylation in TRIM functions. Our systematic approach will allow us to uncover regulatory pathways common to multiple TRIM proteins and to characterize poorly studied members of the TRIM family. In addition to significantly advancing scientific knowledge, this research program has potential applications in protein engineering., agreement title english : TRIM proteins and the SUMO pathway: a systematic and functional analysis, agreement title french : TRIM proteins and the SUMO pathway: a systematic and functional analysis, agreement number : RGPIN, agreement value : 130000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada