CYTOKINE GENE REGULATION BY MODIFICATION OF ARGININE RESIDUES

通过精氨酸残基的修饰来调节细胞因子基因

• 批准号: 7957844
• 负责人: KERRI A MOWEN
• 金额: $ 0.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957844
• 关键词: Allergic; Arginine; Autoimmune Diseases; Biology; Cells; Computer Retrieval of Information on Scientific Projects Database; Cytokine Gene; Data; Event; Funding; Fungal Genome; Gene Expression Regulation; Genetic Transcription; Grant; Immunologic Receptors; Institution; Interleukin-4; Methylation; Modification; Molecular; Positioning Attribute; Production; Protein-arginine deiminase; Receptor Signaling; Research; Research Personnel; Resources; Signal Pathway; Source; T-Cell Receptor; Th2 Cells; United States National Institutes of Health; arginine methyltransferase; cofactor; cytokine; genetic regulatory protein; prevent; promoter; response; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cytokine production by the Th1 and Th2 subsets have been associated with susceptiblity to infectious, allergic, and autoimmune diseases. Understanding the molecular events which control lineage-specific cytokine expression would provide useful tools to modulate the Th1/Th2 response. IL-4 production by Th2 cells is regulated by NFAT and the NFAT cofactor, NIP45. We have shown that arginine methylation of NIP45 facilitates its interaction with NFAT and augments IL-4 transcription. Our data positioned the arginine methyltransferase PRMT1 downstream of the T cell receptor, suggesting that arginine methylation may be an important modification in immune receptor signaling pathways. Arginine methylation is countered by the actions of peptidylarginine deiminase 4 (PAD4). NIP45 methylation is negatively regulated by PAD4 via citrullination of arginine residues, which prevents the ability of NIP45 to be methylated by PRMT1, reducing NIP45-induced IL-4 promoter activity. We hypothesize that through actions on NIP45 and other regulatory proteins that PAD4 controls Th cell cytokine expression.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Th1和Th2亚群产生的细胞因子与感染性、过敏性和自身免疫性疾病的易感性有关。了解控制谱系特异性细胞因子表达的分子事件将为调节Th1/Th2反应提供有用的工具。Th2细胞产生IL-4受NFAT和NFAT辅助因子NIP45的调节。我们已经证明，NIP45的精氨酸甲基化促进了它与NFAT的相互作用，并增强了IL-4的转录。我们的数据将精氨酸甲基转移酶PRMT1定位在T细胞受体下游，这表明精氨酸甲基化可能是免疫受体信号通路中的一个重要修饰。精氨酸甲基化被肽基精氨酸脱亚胺酶4(PAD4)的作用所抵消。PAD4通过精氨酸残基的瓜氨酸化负调控NIP45甲基化，从而阻止NIP45被PRMT1甲基化，从而降低NIP45诱导的IL-4启动子活性。我们推测，通过对NIP45和其他调节蛋白的作用，PAD4控制Th细胞因子的表达。