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Journal of Undergraduate Research

Keywords

targeting superoxide, dismutase-1, cancer, SOD1

College

Physical and Mathematical Sciences

Department

Chemistry and Biochemistry

Abstract

SOD1 is overexpressed in many cancers such as lung adenocarcinoma, non-­ small-­cell lung cancer, and 70% of primary breast cancers. Traditionally, SOD1 is known as an antioxidant in the human body, but only 1% of SOD1 expressed in cells is necessary to keep superoxide radicals below cytotoxic levels, suggesting that SOD1 may have undiscovered functions. One of the known trademarks of cancer is the Warburg Effect defined by up-­regulated glycolysis and down-­ regulated respiration. It is thought that this unique mode of metabolism promotes cancer cell growth. A recent study demonstrated that SOD1 functions to repress respiration through the casein kinase pathway, thereby possibly linking SOD1 to the Warburg Effect and explaining why SOD1 is overexpressed in cancer. We recently found that the 123rd amino acid of SOD1 (a lysine, K123) is modified by acyl groups. K123 is found in the electrostatic loop of SOD1, which is a critical domain responsible for binding copper, a cofactor of SOD1 that allows it to be active. These studies revealed that when SOD1 is acyl modified at lysine 123, it loses its ability to suppress respiration, which would lead to a loss of the Warburg Effect and decreased proliferation of cancer cells (Figure 1). While the effect of acyl modification on SOD1 is clear, we do not yet know how acyl modification disrupts this function of SOD1

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