Department of Pathophysiology, College of Basic Medical Sciences, China Medical University, Shenyang 110122, China.
Department of Clinical Medicine, China Medical University, Shenyang 110122, China.
Biomed Pharmacother. 2024 Sep;178:117147. doi: 10.1016/j.biopha.2024.117147. Epub 2024 Jul 24.
The E2F transcription factor family, whose members are encoded by the E2F1-E2F8 genes, plays pivotal roles in the cell cycle, apoptosis, metabolism, stemness, metastasis, aging, angiogenesis, tumor promotion or suppression, and other biological processes. The activity of E2Fs is regulated at multiple levels, with posttranslational modifications being an important regulatory mechanism. There are numerous types of posttranslational modifications, among which phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, and poly(ADP-ribosyl)ation are the most commonly studied in the context of the E2F family. Posttranslational modifications of E2F family proteins regulate their biological activity, stability, localization, and interactions with other biomolecules, affecting cell proliferation, apoptosis, DNA damage, etc., and thereby playing roles in physiological and pathological processes. Notably, these modifications do not always act alone but rather form an interactive regulatory network. Currently, several drugs targeting posttranslational modifications are being studied or clinically applied, in which the proteolysis-targeting chimera and molecular glue can target E2Fs. This review aims to summarize the roles and regulatory mechanisms of different PTMs of E2F family members in the physiological state and in cancer and to briefly discuss their clinical significance and potential therapeutic use.
E2F 转录因子家族的成员由 E2F1-E2F8 基因编码，在细胞周期、细胞凋亡、代谢、干性、转移、衰老、血管生成、肿瘤促进或抑制以及其他生物学过程中发挥关键作用。E2Fs 的活性在多个层次上受到调节，其中翻译后修饰是一个重要的调节机制。有许多类型的翻译后修饰，其中磷酸化、乙酰化、甲基化、泛素化、SUMO 化、类泛素化和多聚（ADP-核糖）化是 E2F 家族中研究最多的。E2F 家族蛋白的翻译后修饰调节其生物学活性、稳定性、定位以及与其他生物分子的相互作用，影响细胞增殖、细胞凋亡、DNA 损伤等，从而在生理和病理过程中发挥作用。值得注意的是，这些修饰并不总是单独作用，而是形成一个相互作用的调节网络。目前，正在研究或临床应用几种针对翻译后修饰的药物，其中蛋白酶体靶向嵌合体和分子胶可以靶向 E2Fs。本综述旨在总结 E2F 家族成员不同 PTM 在生理状态和癌症中的作用和调节机制，并简要讨论其临床意义和潜在的治疗用途。
