Proteome-wide assessment of the impact of citrullination on the activityof transcription factors in Th2 cells

瓜氨酸化对 Th2 细胞转录因子活性影响的全蛋白质组评估

• 批准号: 10493375
• 负责人: I-CHENG HO
• 金额: $ 21.51万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10493375
• 关键词: Acetylation; Affect; Amino Acids; Attenuated; Autoimmune Diseases; Biological Assay; Cell physiology; Cells; Clinical; Consensus; DNA; DNA Binding; Data; Development; Electrophoretic Mobility Shift Assay; Exploratory/Developmental Grant; Felis catus; Future; GATA3 gene; Genetic Transcription; Goals; Health; Histone Deacetylase; Human; Immune; Immune response; In Vitro; Infection; Invaded; Knowledge; Lymphocyte; Mammals; Mass Spectrum Analysis; Measures; Mediating; Methods; Modification; Mus; NF-kappa B; Pathogenicity; Phosphorylation; Play; Post-Translational Protein Processing; Process; Protein-arginine deiminase; Proteins; Proteome; Proteomics; Protocols documentation; Regulatory T-Lymphocyte; Response Elements; Rest; Role; Set protein; Sodium Chloride; Testing; Th2 Cells; Transcript; Untranslated RNA; chromatin immunoprecipitation; human disease; immune function; improved; innovation; liver development; neutrophil; new therapeutic target; novel strategies; protein function; recruit; tool; transcription factor; transcriptome sequencing

Project Summary Many proteins are modified after they are produced in cells. Such modification can critically influence the function of proteins. One such modification is citrullination, which has been shown to regulate the function of immune cells, including lymphocytes and neutrophils. Abnormal citrullination has been associated with many human diseases, including infection and autoimmune diseases. Thus, manipulating protein citrullination can be beneficial in many clinical settings; however, our knowledge of citrullination is still very limited mainly due to lack of reliable methods for examining the functional impact of citrullination. The objective of this project is to develop a method that can be used to assess the proteome-wide impact of citrullination on the activity of transcriptional regulators in immune cells. A DNA-proteomic platform will be optimized and subsequently used to compare the activity of transcriptional regulators at a proteomic scale between citrullination sufficient and deficient lymphocytes. The approach can be readily modified and applied to other immune cells. Results thus generated very likely will lead to discoveries of novel therapeutic targets of human diseases.

项目摘要 在细胞中产生许多蛋白质后，它们会经过修饰。这种修改会严重影响 蛋白质的功能。一种这样的修改是柠檬化，已证明可以调节 免疫细胞，包括淋巴细胞和中性粒细胞。瓜氨酸异常与许多 人类疾病，包括感染和自身免疫性疾病。因此，操纵蛋白柠檬酸可以是 在许多临床环境中有益；但是，我们对柠檬化的了解仍然非常有限，主要是由于 缺乏可靠的方法来检查柠檬化的功能影响。该项目的目的是 开发一种可用于评估柑橘硫化对蛋白质组的影响的方法 免疫细胞中的转录调节剂。 DNA-蛋白质组平台将被优化，随后使用 比较以柠檬酸之间的蛋白质组学比较转录调节剂的活性，并且 淋巴细胞不足。该方法可以容易修饰并应用于其他免疫细胞。因此 产生的很可能会导致对人类疾病的新型治疗靶标的发现。