E2F转录因子家族,其成员由E2F1-E2F8基因编码,在细胞周期中起着关键作用,凋亡,新陈代谢,stemness,转移,老化,血管生成,肿瘤促进或抑制,和其他生物过程。E2Fs的活性在多个水平上受到调控,翻译后修饰是一种重要的调控机制。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,SUMOylation,Neddylation,和聚(ADP-核糖基)是在E2F家族的背景下最常研究的。E2F家族蛋白的翻译后修饰调节其生物活性,稳定性,本地化,以及与其他生物分子的相互作用,影响细胞增殖,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,这些修改并不总是单独起作用,而是形成一个互动的监管网络。目前,几种靶向翻译后修饰的药物正在研究或临床应用,其中蛋白水解靶向嵌合体和分子胶可以靶向E2Fs。本文旨在总结E2F家族成员的不同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。
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.