Post-translational regulation of the tumor suppressor PDCD4

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Publication Type honors thesis
School or College College of Engineering
Department Biomedical Engineering
Faculty Mentor Katharine Ullman
Creator Uchida, Kimberly Akimi
Title Post-translational regulation of the tumor suppressor PDCD4
Year graduated 2013
Date 2013-12
Description Expression of the tumor suppressor Programmed cell death 4 (PDCD4) is correlated with better survival outcomes in several types of cancer. When PDCD4 is coexpressed with protein arginine methyltransferase 5, however, this trend does not hold true, suggesting that PDCD4 methylation is involved in the loss of the tumor suppressor capabilities of PDCD4. A better understanding of PDCD4-PRMT5 interaction, PDCD4 methylation, and PDCD4 regulation in general may lead to cancer therapies targeted at restoring or maintaining the tumor suppressive function of PDCD4. This study focused on methylation and phosphorylation of PDCD4 under two contexts: the cell cycle and metabolic stress. Using Xenopus Laevis (frog) eggs to generate extract trapped in either interphase or mitosis, we found that the PDCD4-PRMT5 interaction is regulated by the cell cycle. Our results indicate that there may be a component of full-length PDCD4 that occludes the PRMT5 binding site in mitosis in a phosphorylation-dependent manner. Such an inhibitory mechanism may be useful in therapeutically restoring the tumor suppressive function of PDCD4. During metabolic stress and recovery, we found that methylated PDCD4 is regulated by phosphorylation and are currently working to further define the relationships between methylation, phosphorylation, and localization of PDCD4 under these conditions. Exploring these relationships is pertinent to the molecular basis of cancer, especially since the viability of a tumor may be related to its ability to survive during periods of starvation. Future research will be aimed towards completing our understanding of PDCD4-PRMT5 interaction, PDCD4 methylation, and PDCD4 phosphorylation with the eventual hope that the knowledge gained will aid future diagnostics or therapies.
Type Text
Publisher University of Utah
Subject Tumor suppressor proteins - Regulation
Language eng
Rights Management (c) Kimberly Akimi Uchida
Format Medium application/pdf
Format Extent 1,547,724 bytes
Permissions Reference URL https://collections.lib.utah.edu/details?id=1312203
ARK ark:/87278/s6pc6bpw
Setname ir_htoa
ID 205899
Reference URL https://collections.lib.utah.edu/ark:/87278/s6pc6bpw