Miao Yujuan, Zhang Na, Li Fuqing, Wang Fei, Chen Yuyang, Li Fuqiang, Cui Xueli, Zhao Qingzhi, Cai Yong, Jin Jingji
School of Life Sciences, Jilin University, Changchun 130012, China.
Cells. 2025 Jul 17;14(14):1100. doi: 10.3390/cells14141100.
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 its 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 for 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 inhibits AURKB ubiquitination, thereby stabilizing its protein levels. 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 decreased AURKB expression and activity. Consequently, this downregulation suppresses expression of the downstream oncogene c-MYC, ultimately attenuating the malignant proliferation of breast cancer cells. Collectively, our findings reveal a novel mechanism by which lysine acetylation regulates AURKB stability, highlight the significance of the MOF-AURKB-c-MYC axis in breast cancer progression, and suggest potential therapeutic strategies targeting this pathway in clinical settings.
极光激酶B（AURKB）是一种丝氨酸/苏氨酸蛋白激酶，对有丝分裂期间准确的染色体分离和胞质分裂至关重要。AURKB的失调通常表现为其过表达，与包括乳腺癌在内的各种恶性肿瘤有关。然而，其失调的调控机制仍未完全清楚。在这里，我们确定了MOF/MSL复合物（包括组蛋白乙酰转移酶MOF（KAT8））在通过赖氨酸215（K215）乙酰化调节AURKB稳定性方面的关键作用。这种翻译后修饰抑制AURKB泛素化，从而稳定其蛋白质水平。MOF/MSL介导的AURKB稳定促进染色体乘客复合物（CPC）的正确组装，确保有丝分裂的保真度。值得注意的是，抑制MOF会降低AURKB K215乙酰化，导致AURKB表达和活性降低。因此，这种下调抑制了下游癌基因c-MYC的表达，最终减弱了乳腺癌细胞的恶性增殖。总的来说，我们的研究结果揭示了赖氨酸乙酰化调节AURKB稳定性的新机制，突出了MOF-AURKB-c-MYC轴在乳腺癌进展中的重要性，并提出了在临床环境中针对该途径的潜在治疗策略。
