Functional Characterization of Germline and Cancer-specific Protein MAGEB2.

Cancer is a leading cause of death in the United States of America and is a complex disease characterized by uncontrolled proliferation of cells. Current cancer therapies are promoting the use of personalized medicine to treat the disease, thus increasing survival rates. Melanoma antigen genes (MAGEs), a subgroup of cancer-testis antigens (CTAs), are expressed in the male germline and aberrantly in many cancers (Type I) or ubiquitously expressed (Type II). This research focuses on MAGEB2, a virtually understudied Type I MAGE located on the X chromosome. Previous data from our lab indicate that expression of MAGEB2 in normal cells increases cell proliferation, while depletion of MAGEB2 from cancer cells results in lack of cell viability. Based on these data, we hypothesize that MAGEB2 expression provides a proliferative advantage to cancer cells. To determine the signaling pathways modulated by MAGEB2 expression, we performed RNA-Sequencing on cells expressing MAGEB2 and then identified the most upregulated and downregulated genes with significance to cancer. We will validate our gene expression data and perform gene ontology analysis, followed by gain and loss of function studies to determine signaling pathways required for MAGEB2 to cause a proliferative phenotype. Our second approach will determine the proteins associated with MAGEB2. Using immunoprecipitation (IP)/Mass Spectrometry (MS), we have identified binding partners involved in DNA repair, apoptosis, cell cycle regulation, ribosome biogenesis, chromatin maintenance and remodeling, and protein synthesis. Understanding the mechanisms altering MAGEB2 expression can help scientists develop novel therapeutics to treat cancer.