Impact of SUMO Post-translational Modification on Breast Cancer Development

Proteins are subject to post-translational modifications (PTM) that ensure the plethora of unique cellular functions. SUMO-PTM allows proteins to maintain cellular homeostasis and respond to abnormal stressors. SUMO-PTM of proteins is a dynamic reversible process important to cellular biology and normal human physiology. Consistently an imbalance of SUMO-modified proteins (or SUMOylation) can lead to breast cancer development and support onset of metastatic disease. Hence, the long-term objective of our studies is to understand and develop appropriate therapeutics to restore SUMO-PTM balance in breast cancer. At a molecular level, the Small Ubiquitin-like Modifier (SUMO) molecule forms a covalent bond with lysine residues on target proteins with the work of SUMO-specific family of conjugating enzymes including SUMO E3 ligases. Inversely, SUMO-specific protease or deSUMOylase hydrolyze the bond between SUMO and the target protein to maintain the unmodified form of the substrate. Here, we examine protein interactions between novel SUMO E3 ligase and its target protein in breast cancer cells stressed with conventional anti-cancer therapy. Concurrently, we test how excessive SUMO-PTM impacts breast cancer development using a novel genetically engineered mouse model (GEMM). These results can aid in the further understanding of protein function and cellular homeostasis in context of breast cancer development and resistance to conventional anti-cancer therapy.