. Gankyrin is an oncoprotein overexpressed in numerous cancer types and appears to play key roles in regulating cell proliferation, cell migration and epithelial-mesenchymal transition. These roles are primarily due to gankyrin?s numerous protein-protein interactions. The importance of these protein-protein interactions has been demonstrated by either decreasing gankyrin expression levels or directly disrupting its protein-protein interactions, which has resulted in decreased cell proliferation, cell migration and epithelial-mesenchymal transition, as well as disease severity in animal models of numerous cancer types. Therefore, gankyrin has been identified as an intriguing protein in multiple cancer types. However, much of how gankyrin regulates cell proliferation, cell migration and epithelial-mesenchymal transition is poorly understood. The overall goal of this proposal is to further develop our gankyrin-targeting probes which can be utilized to decipher much of gankyrin?s biological role in regulating cancer cell proliferation, migration and epithelial-mesenchymal transition. Furthermore, these probes will help in validating gankyrin as a therapeutic target due to its diverse roles in multiple cancer types. In order to achieve this goal, we are seeking to improve the ability of the cjoc42 scaffold to bind gankyrin and increase efficacy in specific cell-based assays. This proposal will also seek to provide preliminary data about gankyrin?s role in cancer biology, but the primary focus will be to develop and validate our probes as useful in future experiments. Ultimately, this proposal will provide the chemical probes required to fully understand gankyrin?s biological roles which will directly impact therapeutic advancements in multiple cancer types.
This project focuses on the development of some of the first chemical probes to study the protein-protein interactions of gankyrin, an oncoprotein whose overexpression has been identified in certain cancers. These chemical probes will be used in a multidisciplinary approach to understand how gankyrin regulates key biochemical pathways implicated in cancer proliferation, migration and epithelial-mesenchymal transition, as well as understand how inhibiting its interactions with other proteins can be helpful in cancer treatment. This work will ultimately lead to an increased understanding of gankyrin biology as well as determine its role in cancer onset and progression. 1