E2F

E2F refers to a family of transcription factors that play a central role in regulating the cell cycle, particularly the transition from G1 to S phase. In humans, the E2F family comprises several members (commonly E2F1 through E2F8) that can function as transcriptional activators or repressors. Activator E2Fs (notably E2F1–E2F3) typically partner with DP proteins (DP1 or DP2) to bind DNA at E2F-responsive elements in promoters of genes required for DNA replication and S-phase entry. Repressor E2Fs (such as E2F4, E2F5, E2F6) and the atypical E2Fs (E2F7, E2F8) contribute to transcriptional control in various contexts, including quiescence and late S-phase.

Regulation of E2F activity is closely tied to the retinoblastoma (RB) tumor suppressor pathway. In resting cells, pocket proteins RB, p107, and p130 bind E2F/DP complexes and repress transcription. Growth signals activate cyclin-dependent kinases (CDKs), leading to phosphorylation of RB family proteins. This phosphorylation releases E2F, enabling transcription of target genes involved in DNA synthesis, nucleotide metabolism, and cell-cycle progression. E2F1 also has pro-apoptotic functions in response to DNA damage, acting in parallel with p53-dependent pathways.

Target genes of E2F include cyclin E, thymidine kinase, dihydrofolate reductase, PCNA, and several DNA replication factors. Through coordinated control of these genes, E2F integrates cellular growth signals with DNA replication and cell-cycle progression. Dysregulation of the RB–E2F axis is common in cancer and contributes to unchecked proliferation, making E2F a focal point in studies of cell-cycle control and oncogenesis.