CHARACTERIZATION OF NAG EXPRESSION AND FUNCTIONS

NAG 表达和功能的表征

• 批准号: 7960001
• 负责人: CARLA J GUTHRIDGE
• 金额: $ 11.95万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960001
• 关键词: Affect; Anti-Inflammatory Agents; Anti-inflammatory; Autoimmune Diseases; Biomedical Research; Caenorhabditis elegans; Cell physiology; Cells; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Funding; Gene Proteins; Genes; Grant; Homologous Gene; Inflammation; Inflammatory; Institution; MYCN gene; Malignant Neoplasms; Mediating; Molecular; Neuroblastoma; Oklahoma; Patients; Pattern; Play; Process; Protein Isoforms; Proteins; Research; Research Personnel; Resources; Role; Source; System; Tissues; United States National Institutes of Health; anakinra; cell type; interest; mRNA Decay; outcome forecast; tumorigenesis

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. The focus of this proposal is to understand the molecular and cellular functions of neuroblastoma amplified gene product (NAG), an uncharacterized protein with interesting associations to tumorigenesis, inflammation, and development. The NAG gene is co-amplified with MYCN in neuroblastoma cells; however its expression has been correlated with better prognosis in patients with neuroblastoma. NAG also has been shown to interact with interleukin-1 receptor antagonist, a known anti-inflammatory molecule. In C. elegans NAG expression is important for normal development and has been shown to play a role in nonsense-mediated mRNA decay. By understanding how NAG acts to regulate cellular processes, an understanding of how its expression can affect disease processes such as those associated with cancer and inflammatory autoimmune diseases will be appreciated. Our basic hypothesis is that NAG exists as multiple forms which differentially impact cellular processes and development. To understand the impact of these forms on cellular processes and development, we propose to characterize the expression of NAG isoforms in multiple cell types. We anticipate that different patterns of NAG isoforms will be expressed in these different cell types and that the NAG isoforms will have shared and unique functions important for cellular processes characteristic of the tissue system from which those cells are derived. Additionally, we will develop a C. elegans system to study the NAG homologue. We anticipate the NAG homologue expressed in C. elegans will share basic functions analogous to the vertebrate NAG protein.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该提案的重点是了解神经母细胞瘤扩增基因产物（NAG）的分子和细胞功能，这是一种与肿瘤发生、炎症和发展具有有趣关联的未表征的蛋白质。 NAG基因在神经母细胞瘤细胞中与MYCN共同扩增；然而，其表达与神经母细胞瘤患者更好的预后相关。 NAG 还被证明可以与白细胞介素 1 受体拮抗剂（一种已知的抗炎分子）相互作用。 在线虫中，NAG 表达对于正常发育很重要，并且已被证明在无义介导的 mRNA 衰减中发挥作用。 通过了解 NAG 如何发挥作用来调节细胞过程，了解其表达如何影响疾病过程，例如与癌症和炎症性自身免疫性疾病相关的疾病过程，将受到赞赏。 我们的基本假设是 NAG 以多种形式存在，对细胞过程和发育产生不同的影响。 为了了解这些形式对细胞过程和发育的影响，我们建议表征 NAG 同工型在多种细胞类型中的表达。 我们预计不同模式的 NAG 同种型将在这些不同的细胞类型中表达，并且 NAG 同种型将具有对于这些细胞所源自的组织系统的细胞过程特征重要的共享和独特的功能。 此外，我们将开发一个线虫系统来研究 NAG 同源物。 我们预计线虫中表达的 NAG 同源物将具有与脊椎动物 NAG 蛋白类似的基本功能。