Manipulation of the SUMO Activating Enzyme (SAE) by the Viral Oncoprotein, LMP1
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AuthorMcKinnon, Ashton Taylor
MetadataShow full item record
TitleManipulation of the SUMO Activating Enzyme (SAE) by the Viral Oncoprotein, LMP1
AbstractAs a ubiquitous virus, Epstein-Barr virus (EBV) infects 95% of the global population. Although typically asymptomatic, its latency has been shown to cause a variety of different types of cancers, such as Burkitt’s lymphoma and Hodgkin’s lymphoma. Latent Membrane Protein-1 (LMP1) has been shown to be the principle oncoprotein of EBV by facilitating dysregulation of many pathways through both direct interactions and downstream modulation. This project focuses on the direct interactions of LMP1 with the SUMOylation process. SUMOylation is characterized by the addition of a Small Ubiquitin-like Modifier (SUMO) to a target protein. This helps to facilitate cellular growth and proliferation, protein stabilization and turnover, amongst other cellular processes. We hypothesize that LMP1 directly manipulates the SUMO Activating Enzyme/SUMO E1 (SAE) through a variety of mechanisms. This project investigates the interactions of SAE and LMP1 utilizing immunoprecipitations. Our results show that SAE modulation occurs through interactions in a C-Terminal Activating Region (CTAR) -2 dependent manner. Another aspect is understanding the effect LMP1 has on SAE stabilization. This is done by treating LMP1-expressing cells and non-expressing cells with cycloheximide over a set time course. Western blot data shows a steady decrease in the amount of SAE present in non-LMP1-expressing cells, while SAE remains relatively stable in LMP1-expressing cells. Lastly, the lab is interested in how LMP1 affects protein trafficking. This utilizes immunofluorescence to tag proteins of interest in whole cells and visualize them using confocal microscopy. In addition, we use cellular compartmentalization to detect cytosolic and nuclear proteins in comparison to whole cell lysates. Immunofluorescence results show more SAE present in the cytosol of LMP1-expressing cells, while in negative counterparts, we see SAE primarily in the nucleus. This is confirmed in western blot data from compartmentalization experiments. Our findings suggest that LMP1 is capable of interacting with a variety of different proteins, including direct interactions with enzymes involved in the SUMOylation process, specifically SAE. Future work aims to elucidate how LMP1 can affect other enzymes in the SUMOylation process.