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

一种被称为泛素化的生化反应在调节各种各样的过程中起着核心作用，这些过程对几乎所有的生命王国都很重要。泛素与蛋白质的共价连接涉及一类称为泛素连接酶的独特蛋白质，它代表了泛素系统中最丰富的酶。尽管泛素化通常与不需要的蛋白质的降解和处理有关，但泛素化也以不依赖降解的方式参与调节事件。泛素化是可逆的，被称为去泛素酶（deubiquitinases, DUBs）的特定蛋白酶可以在细胞非常精确的区室中，在细胞生命的非常精确的时间，从选定的蛋白质底物中去除泛素。我们的研究计划旨在阐明鲜为人知的dub的生物学意义和作用机制，特别是那些涉及我们基因组物质的功能和保护的dub（包含我们的基因）。最近的研究结果强烈强调，这些知识是理解泛素化如何控制细胞生长和分裂等基本细胞过程以及保护细胞免受危险化学或物理化合物侵害的先决条件。***我们建议发现与基因相关过程有关的特定dub如何在细胞内起作用。为了实现我们的目标，我们将使用我们最近建立的生物化学和分子生物学的前沿方法。我们的研究将描述DUBs的生物学功能和作用机制。将为去泛素化在细胞生长和基因完整性保护中的作用提供新的见解。***我们的研究将产生重大影响，不仅在获得关于基因和细胞功能的新知识方面，而且在促进建立诊断和治疗方法的新技术和工具方面，从而改善加拿大人的健康和加强加拿大的社会经济景观。*****

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.*****