The E2F Family of Proteins

Cloning of the genes that gave rise to the E2F activities revealed that E2F transcription factors are heterodimers composed of a subunit of the E2F gene family and a subunit of the DP gene family. All the E2F and DP proteins, with the exception of the newly identified E2F 7, have both a conserved DNA binding domain (DBD) and a dimerization domain (Dim, see Fig. 12.1). In mammalian systems, there are seven E2F family members and two DP family members (for reviews, see (Attwooll et al., 2004a; Dyson, 1998)). The E2F family members can be divided into four subgroups. The first subgroup includes E2Fs 1-3 and is often referred to as the "activating E2Fs". In addition to the DNA binding and dimerization sequences, these E2F proteins also contain a cdk binding domain and a nuclear localization sequence in the N terminus, and a transcriptional activation domain and an Rb binding sequence in the C terminus (Fig. 12.1). This subgroup of E2F proteins is required for the activation of E2F target genes at the Gl/S transition and is important for proper cell cycle progression. Compound knock-out of E2Fs 1 -3 leads to cell cycle arrest of mouse embryonic fibroblasts (Wu et al., 2001). The second E2F subgroup includes E2Fs 4 and 5 and is often referred to as the "repressive E2Fs". This subgroup of E2F proteins does not have the cdk binding or the nuclear localization sequences in the N terminus but still contains the Rb binding sequence at the C terminus. Consistent with these structural features, this subgroup of E2Fs functions mainly as repressors of E2F target gene expression and can get into the nucleus only when in complex with the

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