ANALYSIS OF ICIL-1RA1 AND NAG INTERACTIONS

ICIL-1RA1 和 NAG 相互作用的分析

• 批准号: 7381640
• 负责人: CARLA J GUTHRIDGE
• 金额: $ 11.14万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381640
• 关键词: ANALYSIS; ICIL; 1RA1; NAG; INTERACTIONS

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. Interleukin-1 receptor antagonists (IL-1Ra) are naturally occurring inhibitors of interleukin-1 (IL-1). Two intracellular forms of IL-1Ra (icIL-1Ra1 and icIL-1Ra3) have been described at the protein level. The precise function of these isoforms is unclear. Studies have demonstrated a role for icIL-1Ra1 as an inhibitor of IL-1-induced p38 MAP kinase activity, NFkB translocation, and IL-6 and IL-8 expression in epithelial cells. Previous data obtained from yeast two-hybrid analysis suggested that icIL-1Ra1 interacts with two intracellular proteins, COP9 signalosome subunit 3 (CSN3) and neuroblastoma amplified gene product (NAG). CSN3 is a component of the COP9 signalosome and its interaction with icIL-1Ra1 leads to an inhibition of CK2 and PKD kinases that associate with the signalosome complex. NAG is co-amplified along with MYCN in high grade neuroblastomas, however the normal function of the NAG protein is unknown. We hypothesize that icIL-1Ra1 and NAG play a crucial role in the regulation of cellular processes associated with IL-1 signaling. To address this hypothesis we initiated experiments examining the interaction of icIL-1Ra1 and NAG in relevant cell systems. Molecular tools were generated that allowed us to reconfirm the interaction of NAG and icIL-1Ra1 in relevant cell systems. Over-expression and knock-down expression systems have been designed and used to examine the effect of perturbing the expression of NAG and icIL-1Ra1 on global gene expression. Gene expression changes identified by microarray analysis have helped to identify candidate pathways linking NAG and icIL-1Ra1 to common physiological processes. The relevance of this linkage is currently unde

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。 IL-1 受体拮抗剂 (IL-1Ra) 是天然存在的 IL-1 (IL-1) 抑制剂。 IL-1Ra 的两种细胞内形式（icIL-1Ra1 和 icIL-1Ra3）已在蛋白质水平上得到描述。这些亚型的确切功能尚不清楚。研究证明 icIL-1Ra1 作为 IL-1 诱导的 p38 MAP 激酶活性、NFkB 易位以及上皮细胞中 IL-6 和 IL-8 表达的抑制剂。之前从酵母双杂交分析中获得的数据表明，icIL-1Ra1 与两种细胞内蛋白、COP9 信号体亚基 3 (CSN3) 和神经母细胞瘤扩增基因产物 (NAG) 相互作用。 CSN3 是 COP9 信号体的一个组成部分，它与 icIL-1Ra1 的相互作用会抑制与信号体复合物相关的 CK2 和 PKD 激酶。在高级神经母细胞瘤中，NAG 与 MYCN 共同扩增，但 NAG 蛋白的正常功能尚不清楚。我们假设 icIL-1Ra1 和 NAG 在调节与 IL-1 信号传导相关的细胞过程中发挥着至关重要的作用。为了解决这个假设，我们启动了实验来检查相关细胞系统中 icIL-1Ra1 和 NAG 的相互作用。分子工具的产生使我们能够重新确认 NAG 和 icIL-1Ra1 在相关细胞系统中的相互作用。过表达和敲低表达系统已被设计并用于检查扰乱 NAG 和 icIL-1Ra1 表达对整体基因表达的影响。通过微阵列分析确定的基因表达变化有助于确定将 NAG 和 icIL-1Ra1 与常见生理过程联系起来的候选途径。此链接的相关性目前正在研究中