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Show SCHOOL OF MEDICINE AND HEALTH SCIENCES UNDERGRADUATE RESEARCH ABSTRACTS Katharine S. Ullman THE CELL CYCLE REGULATION OF TUMOR SUPPRESSOR PDCD4 AND ITS INTERACTION WITH PRMT5 Kimberly Akimi Uchida (Katharine S. Ullman) Department of Bioengineering, Department of Oncological Sciences, Huntsman Cancer Institute University of Utah Programmed cell death 4 (PDCD4) loses its function as a tumor suppressor when co-expressed with a specific binding partner, protein arginine methyltransferase-5 (PRMT5). A better understanding of the regulation of PDCD4-PRMT5 interaction may lead to cancer therapies targeted at restoring the tumor suppressive function of PDCD4. Using Xenopus laevis (frog) eggs to generate extract trapped in either interphase or mitosis, w e found that PDCD4-PRMT5 interaction is regulated by the cell cycle. Full-length PDCD4 bound PRMT5 more robustly in interphase than in mitosis. However, a truncated version of PDCD4, that retained the PRMT5 binding site, bound PRMT5 equally in interphase and mitosis (See Figure).These results indicate that there may be a component of full-length PDCD4 that occludes the PRMT5 binding site in mitosis. Furthermore, w e found that both full-length and truncated PDCD4 are preferentially phos-phorylated in mitosis, but preferentially methylated in interphase. From these results w e speculate that phosphorylation of PDCD4 in mitosis allows PDCD4 to fold upon itself and effectively block the PRMT5 binding site. Additionally, phosphorylation may prevent methylation even when PRMT5 can bind PDCD4, explaining the lack of PDCD4 methylation in mitosis. Such an inhibitory mechanism may be useful in therapeutically restoring the tumor suppressive function of PDCD4. Future research will be aimed towards completing our understanding of PDCD4-PRMT5 interaction in the cell cycle, such as proving our model in human cells. GST-Full- Length-PDCD4 GST (Neg. Con.) M M GST-N-Term- PDCD4 I M Egg Extract (Pos. Con.) M PRMT5 GST-PDCD4 134 |