Unraveling the function and the mechanism of action of the deubiquitinase MYSM1

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A biochemical reaction called ubiquitination plays a central role in regulating a wide variety of processes that are important for virtually all kingdoms of life. The covalent attachment of ubiquitin to proteins involves a distinct class of proteins called ubiquitin ligases, which represent the most abundant enzymes of the ubiquitin system. Although most often associated with degradation and disposal of unwanted proteins, ubiquitination is also involved in regulatory events in degradation-independent manner. Ubiquitination is reversible and specific proteases, called deubiquitinases (DUBs), remove ubiquitin from selected protein substrates in very precise compartments of our cells and at very precise times of their life. Our research program aims at elucidating the biological significance and mechanisms of action of poorly understood DUBs, especially those implicated in the functioning and protection of our genomic material (harboring our genes). Recent findings have strongly emphasized that such knowledge is prerequisite for understanding how ubiquitination controls fundamental cellular processes such as cell growth and division and protection from dangerous chemical or physical compounds. We propose to discover how specific DUBs, which were implicated in gene-associated processes, work within the cells. To accomplish our objectives, we will use cutting-edge approaches in biochemistry and molecular biology that we recently established. Our investigation will delineate the biological functions and mechanisms of action of DUBs. New insights will be provided into the role of deubiquitination in cell growth and protection of gene integrity. Our studies will have a major impact, not only in terms of acquiring a novel knowledge on gene and cell function, but also in facilitating the establishment of novel technologies and tools for diagnostic and treatment approaches, thus improving Canadians health and enhancing the socio-economical landscape in Canada.