CHARACTERIZATION OF NAG EXPRESSION AND FUNCTIONS

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。 这项建议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，NAG是一种与肿瘤发生、炎症和发展有关的未知蛋白质。在神经母细胞瘤细胞中，NAG基因与MYCN共扩增，但其表达与神经母细胞瘤患者较好的预后相关。NAG还被证明与白介素1受体拮抗剂相互作用，白介素1受体拮抗剂是一种已知的抗炎分子。在线虫中，NAG的表达对正常发育很重要，并已被证明在无意义介导的mRNA衰退中发挥作用。通过了解NAG如何调节细胞过程，了解其表达如何影响疾病过程，如与癌症和炎症性自身免疫性疾病相关的过程，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异构体在多种细胞类型中的表达。我们预计，不同模式的NAG亚型将在这些不同的细胞类型中表达，并且NAG亚型将具有共同和独特的功能，这些功能对于这些细胞来源的组织系统特有的细胞过程非常重要。此外，我们将开发一个线虫系统来研究NAG同源物。我们预计在线虫中表达的NAG同源物将具有与脊椎动物NAG蛋白类似的基本功能。

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.