Posttranslational modifications of E2F family members in the physiological state and in cancer: Roles, mechanisms and therapeutic targets
Mingyang Sun, Yitong Ji, Guo‐Jun Zhang, Yang Li, Fengming Dong, Tianyi Wu
Abstract
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. • Different posttranslational modifications of E2Fs mediated by various enzymes. • Roles and regulatory mechanisms of posttranslational modifications on E2Fs. • Crosstalk of various posttranslational modifications of E2Fs. • Potential value of E2F posttranslational modifications in cancer therapy.