An Atypical Oncogene Within the Atypical E2Fs

E2F transcription factors are critical components of the transcriptional machinery that modulates the expression of genes required for DNA synthesis and mitosis during the cell cycle. The mammalian E2F factors have been broadly classified into classical activators (E2F1-3) and repressors (E2F4-6). An additional, recently identified branch of this family is composed of two members, E2F7 and E2F8, which are designated as atypical E2Fs because of their structural differences when compared with canonical E2Fs. These atypical E2Fs harbor two DNA-binding domains instead of one, do not require a dimerization partner (DP) to bind to DNA, and regulate transcription independently of retinoblastoma (RB) (1). E2F7 and E2F8 share many transcriptional targets and can form homo- and heterodimers at their target promoters. Atypical E2Fs are thought to play overlapping roles because, whereas E2f7- or E2f8-null mice developed normally, deletion of both genes caused lethality during midgestation in murine embryos as a consequence of massive apoptosis and vascular defects (2). Both E2F7 and E2F8 are able to regulate angiogenesis and lymphangiogenesis in a cell-cycle independent manner by controlling critical regulators such as VEGF, CCBE1, and FLT4 (3,4), although whether these targets are responsible for the vascular defect in E2F7/8 mutant embryos is not clear at present.