CHARACTERIZATION OF NAG EXPRESSION AND FUNCTIONS

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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.