Wang Lei, Zhao Liting, Lan Xintian, Zhu Ming, Tan Yiying, Luo Haoming, Wu Donglu
School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China.
Int J Mol Sci. 2025 May 29;26(11):5257. doi: 10.3390/ijms26115257.
Lysine acetyltransferase 8 (KAT8) is a member of the MYST family of histone acetyltransferases. It catalyzes the acetylation of histone H4 at lysine 16 (H4K16ac) and non-histone proteins. Abnormal upregulation or downregulation of KAT8 and its associated H4K16ac have been observed in malignant tumors, suggesting its close association with tumorigenesis and progression. Characterized by structural diversity and multi-target mechanisms, natural agents have been increasingly shown to possess significant antitumor activity. This review focuses on KAT8, summarizing its molecular mechanisms in regulating tumor development by catalyzing substrate protein acetylation, which impacts tumor cell proliferation, cell cycle regulation, apoptosis, DNA damage repair, and autophagy. It also systematically discusses the pharmacological activities and molecular mechanisms of small-molecule agents that target KAT8 to inhibit tumor proliferation, including natural compounds, synthetic drugs, and non-coding RNAs.
赖氨酸乙酰转移酶8(KAT8)是组蛋白乙酰转移酶MYST家族的成员。它催化组蛋白H4赖氨酸16位点(H4K16ac)的乙酰化以及非组蛋白的乙酰化。在恶性肿瘤中已观察到KAT8及其相关的H4K16ac异常上调或下调,表明其与肿瘤发生和进展密切相关。天然药物具有结构多样性和多靶点作用机制,越来越多地显示出具有显著的抗肿瘤活性。本综述聚焦于KAT8,总结其通过催化底物蛋白乙酰化来调节肿瘤发展的分子机制,这一过程影响肿瘤细胞增殖、细胞周期调控、细胞凋亡、DNA损伤修复和自噬。此外,还系统地讨论了靶向KAT8以抑制肿瘤增殖的小分子药物的药理活性和分子机制,包括天然化合物、合成药物和非编码RNA。