E2F1 is a cell cycle-regulated transcription factor located on chromosome 20 1 that controls G1/S phase progression by binding cooperatively with DP proteins to E2 recognition sites in target gene promoters 23. E2F1 preferentially binds retinoblastoma protein (RB1) in a cell cycle-dependent manner 23, and its activity is modulated by protein-protein interactions and post-translational modifications. Calcineurin stabilizes E2F1 through dephosphorylation at serine-403, preventing FBXW7-mediated ubiquitination and degradation 4, while Hsp90 chaperone facilitates E2F1/2 nuclear accumulation and transcriptional activity 5. Beyond proliferation, E2F1 mediates p53-dependent apoptosis through multiple pathways 6, providing a tumor-suppressive checkpoint. In cancer, E2F1 becomes pathologically overexpressed and drives malignancy. For instance, in ovarian cancer, NSUN2-mediated m5C modification increases E2F1 mRNA stability, establishing a positive feedback loop that promotes oncogenic transcription 7. Similarly, DLGAP5 stabilizes E2F1 via USP11-mediated deubiquitination in bladder cancer, creating another oncogenic feedback circuit 8. E2F1 also promotes angiogenesis by activating arterial markers EphrinB2 and HEY2, a process antagonized by DNMT3A 9. These findings underscore E2F1's dual role as both proliferative driver and apoptotic regulator, with dysregulation contributing significantly to cancer pathogenesis.