A proteomics-based approach for the analysis of sumoylation patterns in normal and apoptotic human cells

一种基于蛋白质组学的方法，用于分析正常和凋亡人类细胞中的苏酰化模式

• 批准号: 326812-2006
• 负责人: Berthoux, Lionel
• 金额: $ 2.26万
• 依托单位: Université du Québec à Trois-Rivières
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=397425
• 关键词: proteomics; based; approach; analysis; sumoylation

Sumoylation, a protein modification, is defined by the covalent and reversible attachment of the protein SUMO to the target protein. This pathway is required for mammalian cell survival, arguing for its critical role.  Only small amounts of sumoylated proteins are found modified in natural conditions, making their identification difficult. Nonetheless, dozens of cellular and viral proteins haven been shown to be modified by SUMO, and it is likely that many more remain to be identified. Although the outcome of sumoylation has been well characterized for individual proteins, the importance of sumoylation (as a pathway) in specific cellular functions is poorly understood. The proposed research program will use proteomic tools for the purification of human sumoylated proteins involved in specific pathways. SUMO targets will be identified, then we will use genetic tools to investigate the impact of sumoylation for these individual proteins. This proteomics/functional dual approach will be first applied to investigate the relationships between sumoylation and apoptosis (programmed cell death) as well as cell cycle progression. Specifically, we will identify proteins that are either sumoylated or desumoylated at various cell cycle stages and following apoptosis induction. Then we will analyze in details the role of sumoylation for these proteins. We expect that this project will identify new protein targets of SUMO and show the role of this modification in the normal and apoptotic cell. This work might also identify new targets for cancer therapies aimed at regulating the cell cycle. On the long term, we will apply this approach to investigate the importance of sumoylation in other contexts such as viral infections.

Sumoylation 是一种蛋白质修饰，是通过蛋白质 SUMO 与靶蛋白的共价和可逆连接来定义的。该途径是哺乳动物细胞生存所必需的，因此具有关键作用。  仅发现少量的苏酰化蛋白质在自然条件下发生修饰，这使得它们的鉴定变得困难。尽管如此，数十种细胞和病毒蛋白已被证明可以被 SUMO 修饰，而且可能还有更多蛋白有待鉴定。尽管对于单个蛋白质来说，SUMO 化的结果已经得到了很好的表征，但 SUMO 化（作为一种途径）在特定细胞功能中的重要性却知之甚少。拟议的研究计划将使用蛋白质组学工具来纯化参与特定途径的人类苏酰化蛋白质。 SUMO 目标将被确定，然后我们将使用遗传工具来研究 SUMO 化对这些单个蛋白质的影响。这种蛋白质组学/功能双重方法将首先用于研究苏酰化和细胞凋亡（程序性细胞死亡）以及细胞周期进程之间的关系。具体来说，我们将鉴定在不同细胞周期阶段和细胞凋亡诱导后被苏酰化或去苏酰化的蛋白质。然后我们将详细分析这些蛋白质的SUMO化作用。我们预计该项目将鉴定 SUMO 的新蛋白质靶标，并展示这种修饰在正常细胞和凋亡细胞中的作用。这项工作还可能确定旨在调节细胞周期的癌症治疗的新靶点。从长远来看，我们将应用这种方法来研究苏素化在其他情况（例如病毒感染）中的重要性。