Function and mechanism of a novel SUMO protease

新型SUMO蛋白酶的功能和机制

• 批准号: 8459248
• 负责人: LIAN LI
• 金额: $ 29.64万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8459248
• 关键词: Alzheimer' s Disease; Apoptosis; Biochemical; Biological; Cell physiology; Cells; Complex; Cysteine; Cysteine Protease; Cytoprotection; DNA Repair; Data; Development; Diabetes Mellitus; Disease; Enzymes; Eukaryotic Cell; Family; Functional disorder; Genetic; Goals; Health; Heart Diseases; Human; Huntington Disease; Impairment; Investigation; Knowledge; Link; Malignant Neoplasms; Methionine; Mitochondria; Mitochondrial Proteins; Molecular; Mus; Mutation; Nerve Degeneration; Neurodegenerative Disorders; Nuclear Proteins; Oxidation-Reduction; Oxidative Stress; Parkinson Disease; Pathogenesis; Peptide Hydrolases; Phosphorylation; Physiological; Physiology; Play; Post-Translational Protein Processing; Process; Proteins; Proteomics; RNA Binding; Reaction; Regulation; Research; Role; Signal Pathway; Signal Transduction; Stroke; Structure-Activity Relationship; Test Result; Testing; Therapeutic; Transcriptional Regulation; Ubiquitin; Ubiquitination; Up-Regulation; age related; base; early onset; follow-up; human disease; male; novel; oxidation; protein protein interaction; protein transport; public health relevance; response

DESCRIPTION (provided by applicant): Sumoylation, the covalent attachment of small ubiquitin-like modifier (SUMO) to cellular proteins, has emerged as an important signaling mechanism for regulating protein activity, stability/degradation, subcellular localization, and protein-protein interaction. Like ubiquitination, sumoylation is a dynamic and reversible post-translational modification that is controlled by opposing actions of sumoylating enzymes and SUMO proteases (also known as desumoylating enzymes). Sumoylation plays a critical role in regulation of numerous cellular processes, from transcriptional regulation and DNA repair to protein trafficking, mitochondrial dynamics, and apoptosis. Dysregulated sumoylation has been implicated in a variety of human diseases, including cancer, diabetes, heart disease, and neurodegenerative disorders such as Alzheimer and Parkinson diseases. Despite increasing evidence supporting the importance of sumoylation to human health and disease, our knowledge about the sumoylation/desumoylation machinery components and their cellular functions is limited. In this project, the applicant's team will use a combination of biochemical, proteomic, cell biological, and mouse genetic approaches to study a novel SUMO protease and its signaling role in cellular defense against oxidative stress and apoptosis. The results of the proposed studies should advance our knowledge of the fundamental mechanisms governing SUMO signaling in all eukaryotic cells and provide a molecular basis for understanding and treating a diverse array of human diseases that involve dysregulated sumoylation.

描述（由申请人提供）：Sumoylation，小型泛素样修饰剂（SUMO）与细胞蛋白的共价附着已成为调节蛋白质活性，稳定性/降解，亚细胞局部定位和蛋白质蛋白质相互作用的重要信号机制。像泛素化一样，Sumoylation是一种动态和可逆的翻译后修饰，它通过相反的sumoylating酶和Sumo蛋白酶（也称为Desumoylating酶）来控制。 Sumoylation在调节众多细胞过程中起着至关重要的作用，从转录调控和DNA修复到蛋白质运输，线粒体动力学和凋亡。 sumoylation的失调与多种人类疾病有关，包括癌症，糖尿病，心脏病和神经退行性疾病，例如阿尔茨海默氏病和帕金森病。尽管越来越多支持Sumoylation对人类健康和疾病的重要性的证据，但我们对Sumoylation/desumoylation机械组件及其细胞功能的了解仍然有限。在该项目中，申请人的团队将使用生化，蛋白质组学，细胞生物学和小鼠遗传方法的组合来研究新型SUMO蛋白酶及其在抗氧化应激和凋亡中的细胞防御中的信号传导作用。拟议的研究的结果应提高我们对所有真核细胞中SUMO信号传导的基本机制的了解，并为理解和治疗各种人类疾病的分子基础提供了分子基础，这些疾病涉及sumoylation失调。