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瓣状核酸内切酶1(Flap endonuclease 1, FEN1)是一种结构特异性的多功能核酸内切酶，在DNA复制、修复及基因组稳定性维持中发挥核心作用。FEN1表达异常与多种恶性肿瘤的发生、进展及治疗响应密切相关。翻译后修饰（Post-translational modifications, PTMs）是调控蛋白质功能的关键机制，在FEN1活性与稳定性中发挥重要作用。具体而言，FEN1可受磷酸化、SUMO化、泛素化、乙酰化、甲基化、O-GlcNAc糖基化、琥珀酰化、乳酸化及ADP-核糖基化等多种PTMs调控，这些修饰形成的交互网络共同决定FEN1的生物学功能。本文从翻译后修饰调控网络出发，阐述了FEN1功能紊乱在肿瘤发生中的双重作用及其在精准治疗中的转化前景，可为恶性肿瘤的早期诊断与个体化治疗提供理论框架。
Abstract：Flap endonuclease 1(FEN1) is a structure-specific multifunctional endonuclease that plays a central role in DNA replication, repair, and the maintenance of genome stability. Dysregulation of FEN1 expression is closely associated with the initiation, progression, and therapeutic response of various malignancies. Post-translational modifications(PTMs) serve as key mechanisms regulating FEN1 activity and stability. Specifically, FEN1 is precisely regulated by multiple PTMs, including phosphorylation, SUMOylation, ubiquitination, acetylation, methylation, O-GlcNAcylation, succinylation, lactylation, and ADP-ribosylation. The interactive network formed by these modifications collectively determines the biological function of FEN1. Starting from the PTM regulatory network, this review systematically elucidates the dual role of FEN1 dysfunction in tumorigenesis and its translational prospects in precision cancer therapy, providing a theoretical framework for the early diagnosis and personalized treatment of malignancies.
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基本信息:
中图分类号:R730
引用信息:
[1]刘锦,赵莉文,曾扬能,等.FEN1翻译后修饰调控网络及其在肿瘤发生与精准治疗中的作用[J].赣南医科大学学报().
基金信息:
国家自然科学基金地区项目(82560170)
2026-06-29
2026-06-29
2026-06-29