Histone Acetyltransferase MOF-Mediated AURKB K215 Acetylation Drives Breast Cancer Cell Proliferation via c-MYC Stabilization

Aurora kinase B (AURKB), a serine/threonine protein kinase, is essential for accurate chromosome segregation and cytokinesis during mitosis. Dysregulation of AURKB, often characterized by overexpression, has been implicated in various malignancies, including breast cancer. However, the mechanisms governing its dysregulation remain incompletely understood. Here, we identify a pivotal role of the MOF/MSL complex, which includes the histone acetyltransferase MOF (KAT8), in modulating AURKB stability through acetylation at lysine 215 (K215). This post-translational modification prevents AURKB ubiquitination, thereby stabilizing its expression. MOF/MSL-mediated AURKB stabilization promotes the proper assembly of the chromosomal passenger complex (CPC), ensuring mitotic fidelity. Notably, inhibition of MOF reduces AURKB K215 acetylation, leading to a decline in both AURKB expression and activity. Consequently, this downregulation suppresses the expression of the downstream target c-MYC, ultimately attenuating the malignant proliferation of breast cancer cells. Collectively, our findings reveal a novel mechanism by which lysine acetylation governs AURKB stability, highlight the significance of the MOF-AURKB-c-MYC axis in breast cancer progression, and propose potential therapeutic strategies targeting this pathway in clinical settings.