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 许多蛋白质在细胞中产生后被修饰。这种修改可能会严重影响 蛋白质的功能。一种这样的修饰是瓜氨酸化，它已被证明调节 免疫细胞，包括淋巴细胞和中性粒细胞。异常的瓜氨酸化与许多 人类疾病，包括感染和自身免疫性疾病。因此，操控蛋白质的瓜氨酸化可以 有益于许多临床环境；然而，我们对瓜氨酸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瓜氨酸化的功能影响。这个项目的目标是 建立一种方法，可以用来评估瓜氨酸化对蛋白组学活性的影响 免疫细胞中的转录调节因子。DNA-蛋白质组平台将被优化并随后使用 在蛋白质组学水平上比较瓜氨酸化充分和充分的转录调节因子的活性 淋巴细胞缺乏。这种方法可以很容易地修改并应用于其他免疫细胞。结果如下 很可能会导致人类疾病新的治疗靶点的发现。