CHARACTERIZATION OF NAG EXPRESSION AND FUNCTIONS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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，NAG是一种与肿瘤发生，炎症和发展有有趣关联的未表征蛋白质。 NAG基因在神经母细胞瘤细胞中与MYCN共扩增;然而，其表达与神经母细胞瘤患者的良好预后相关。 NAG还显示与白细胞介素-1受体拮抗剂（一种已知的抗炎分子）相互作用。 In C.线虫NAG表达对于正常发育是重要的，并且已经显示在无义介导的mRNA衰减中起作用。 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，这些形式对细胞过程和发育有不同的影响。 为了了解这些形式对细胞过程和发育的影响，我们建议在多种细胞类型中表征NAG亚型的表达。 我们预期不同模式的NAG同种型将在这些不同的细胞类型中表达，并且NAG同种型将具有对于那些细胞所来源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C。elegans系统来研究NAG同源物。 我们预期在C.线虫将共享与脊椎动物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.