E2F is a group of genes that codifies a family of transcription factors in higher eukaryotes. Three of them are activators, E2F1,2 and E2F3a, six others act as suppressors, E2F3b, E2F4-8. All of them are involved in the cell cycle regulation and synthesis of DNA in mammalian cells, e2Fs as TFs bind to the TTTCCCGC consensus binding site in the target promoter sequence. X-ray crystallographic analysis has shown that the E2F family of transcription factors has a similar to the winged-helix DNA-binding motif. E2F family members play a role during the G1/S transition in mammalian. DNA microarray analysis reveals unique sets of target promoters among E2F family members suggesting that each protein has a role in the cell cycle. Among E2F transcriptional targets are cyclins, CDKs, checkpoints regulators, DNA repair, nonetheless, there is a great deal of redundancy among the family members. Mouse embryos lacking E2F1, E2F2, and one of the E2F3 isoforms, the E2F family is generally split by function into two groups, transcription activators and repressors. Activators such as E2F1, E2F2, E2F3a promote and help carryout the cell cycle, while repressors inhibit the cell cycle, yet, both sets of E2F have similar domains. E2F1-6 have DP1,2 heterodimerization domain which allows them to bind to DP1 or DP2, binding with DP1,2 provides a second DNA binding site, increasing E2F binding stability. Most E2F have a protein binding domain. Pocket proteins such as pRB and related proteins p107 and p130, in activators, E2F binding with pRB has been shown to mask the transactivation domain responsible for transcription activation. In repressors E2F4 and E2F5, pocket protein binding mediates recruitment of repression complexes to silence target genes, e2F6, E2F7, and E2F8 do not have pocket protein binding sites and their mechanism for gene silencing is unclear. Cdk4/cyclin D and cdk2/cyclin E phosphorylate pRB and related pocket proteins allowing them to disassociate from E2F, activator E2F proteins can then transcribe S phase promoting genes. In REF52 cells, overexpression of activator E2F1 is able to push quiescent cells into S phase, while repressors E2F4 and 5 do not alter cell proliferation, they mediate G1 arrest. E2F activator levels are cyclic, with maximal expression during G1/S, in contrast, E2F repressors stay constant, especially since they are often expressed in quiescent cells. Specifically, E2F5 is only expressed in differentiated cells in mice. The balance between repressor and activator E2F regulate cell cycle progression, when activator E2F family proteins are knocked out, repressors become active to inhibit E2F target genes
Image: E2F family member
Overview of signal transduction pathways involved in apoptosis.