Based on limited published evidence, MAGEA2B is a MAGE family member that suppresses p53 and p73 transcriptional activity by recruiting HDAC3 to p53 sites and negatively regulating PML-mediated p53 activation. It enhances ubiquitin ligase activity of TRIM28, promoting p53 ubiquitination. MAGEA2B represses PML acetylation and sumoylation. The protein is recognized as a melanoma-associated antigen by cytolytic T-lymphocytes 1 and promotes melanoma cell viability in vitro. A systems biology analysis identified MAGEA2B as an upregulated hub gene in oxaliplatin-resistant colorectal cancer 2, suggesting involvement in tumor progression and chemotherapy resistance.