YALE UNIVERSITY
Grant: $413,750 - National Institutes of Health - Sep. 25, 2009
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Award Description: This proposal is based on the observation that ?-catenin protein is localized to the leading edge of migrating astrocytes. In preliminary work we have examined this increase and determined it to be dependent upon new protein synthesis. Since cadherin/catenin signaling is known to be important in cell adhesion and migration we will attempt to characterize the molecular mechanism controlling the synthesis and localization of ?-catenin protein in migrating astrocytes. In addition, ?-catenin is a known oncogene and there is good evidence that the level of ?-catenin protein is increased in some cancers. Therefore, by identifying the molecular mechanism regulating the synthesis of ?-catenin, we hope to generate potential therapeutic targets to inhibit ?-catenin synthesis. In this regard, we have identified a sequence in the mRNA encoding ?-catenin that may regulate its translation. In addition, this sequence is present in mRNA encoding other proteins known to play a role in glioblastoma pathology. Based upon our preliminary data, we hypothesize that the mRNA-binding protein CPEB1 is regulating translation of mRNA encoding proteins mediating astrocyte migration. Directional migration requires the concise recruitment of specific proteins to discrete cellular compartments and we will determine if local mRNA translation plays a role in targeting proteins to the leading edge of migrating astrocytes. We will utilize a simple but elegant in vitro wound assay to show the localization of endogenous ?-catenin mRNA. In addition, we will use reporter constructs that encode fluorescent protein and mRNA to track protein synthesis and mRNA localization respectively. Finally, we will use bioinformatics as well as biochemistry to identify the cohort of mRNAs that might be co-translationally regulated by CPEB1. We are specifically interested in understanding the role of CPEB1 in astrocytes due to the important role astrocytes play in the response to brain injury, and we hope to use this knowledge to inhibit glioblastoma tumor progression in vitro and in vivo.
Project Description: See Award Description
Jobs Summary: None (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 25, 2009. Help expand these official descriptions using the wiki below.
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