E2F transcription factor family (E2F)

The E2F transcription factor family is a group of proteins (E2F1-E2F8) that serve as master regulators of the mammalian cell cycle, particularly the transition from G1 to S phase. These factors are categorized into activators (E2F1-3a) and repressors (E2F3b-8), which coordinately control the expression of genes required for DNA synthesis, replication, and repair [1, 3]. In healthy cells, E2F activity is tightly regulated by the Retinoblastoma (Rb) protein, which binds and inhibits activator E2Fs until phosphorylated by cyclin-dependent kinases (CDK4/6) [11, 18]. In many cancers, this regulatory axis is disrupted through Rb mutation or CDK4/6 overactivity, leading to an uncontrolled E2F-driven transcriptional program that fuels malignant proliferation [2, 22]. Therapeutic strategies targeting this pathway include the widely used CDK4/6 inhibitors, which indirectly suppress E2F activity, as well as experimental small molecules like HLM006474 that directly disrupt E2F DNA binding [17, 18]. Emerging approaches also explore E2F-targeted PROTACs and gene signatures as biomarkers to predict treatment response in aggressive tumors [9, 20].

Other names

E2F familyE2F proteinsE2F-driven transcriptional programE2F transcription factors

Direct inhibition of E2F-DNA binding, disruption of E2F-DP heterodimerization, or indirect suppression via CDK4/6-mediated inhibition of Rb phosphorylation.