Role of the deubiquitinase USP16 in cell cycle progression

去泛素酶 USP16 在细胞周期进程中的作用

• 批准号: 355814-2010
• 负责人: Affar, ElBachir
• 金额: $ 2.4万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=527906
• 关键词: Role; deubiquitinase; USP16; cell; cycle

Ubiquitination is an essential biochemical process which occurs in all cells of our body. This process consists of the attachment of a small protein, called ubiquitin, to various cellular proteins. This labeling system marks the target proteins as unwanted (or no longer needed), and induces their degradation by a molecular machine called the "proteasome". Interestingly it has recently been realized that ubiquitination can also cause changes in the function and properties of the targeted protein without any degradation. Moreover we have now started to appreciate that ubiquitination is a dynamic process and that certain enzymes, called deubiquitinases (DUBs), ensure the timely removal of ubiquitin from proteins. In fact, the functional interaction between ubiquitination and deubiquitination allows cells to tightly regulate protein function. With this capability, the ubiquitin system executes and/or regulates many cellular processes, and these include cellular proliferation, genome expression and repair. The goal of my research is to determine how DUBs regulate protein function, a subject about which very little is currently known. USP16 is one DUB that possesses unique characteristics, and is likely to play a fundamental role in cell proliferation. I plan to use molecular and cellular biology approaches to characterize the biological function and mechanism of action of USP16. This will not only shed new light on the mechanisms that govern normal cellular processes, but will also help in furthering our understanding of disease development.

泛素化是一个重要的生化过程，发生在我们身体的所有细胞中。这个过程包括一种叫做泛素的小蛋白质与各种细胞蛋白质的结合。这种标记系统将靶蛋白标记为不需要的（或不再需要的），并通过称为“蛋白酶体”的分子机器诱导其降解。有趣的是，最近人们意识到，泛素化也可以引起靶蛋白的功能和性质的变化，而不会发生任何降解。此外，我们现在已经开始认识到，泛素化是一个动态的过程，某些酶，称为去泛素化酶（DUBs），确保及时从蛋白质中去除泛素。事实上，泛素化和去泛素化之间的功能相互作用允许细胞严格调节蛋白质功能。利用这种能力，泛素系统执行和/或调节许多细胞过程，这些过程包括细胞增殖、基因组表达和修复。我研究的目标是确定DUBs如何调节蛋白质功能，这是一个目前知之甚少的主题。USP 16是一种具有独特特性的DUB，可能在细胞增殖中发挥重要作用。我计划使用分子和细胞生物学方法来表征USP 16的生物学功能和作用机制。这不仅将为控制正常细胞过程的机制提供新的线索，还将有助于我们进一步了解疾病的发展。