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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要许多蛋白质在细胞中产生后会被修饰。这种修改可以严重影响蛋白质的功能。其中一种修饰是瓜氨酸化，它已被证明可以调节免疫细胞，包括淋巴细胞和中性粒细胞。异常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，操纵蛋白质瓜氨酸化可以是在许多临床环境中有益；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。该项目的目标是开发一种可用于评估瓜氨酸化对蛋白质组活性的影响的方法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比较瓜氨酸化充分和瓜氨酸化之间蛋白质组水平上的转录调节因子的活性淋巴细胞缺乏。该方法可以很容易地修改并应用于其他免疫细胞。结果如此产生的结果很可能会导致人类疾病新治疗靶点的发现。