Identification and characterization of E2F7, a novel mammalian E2F family member capable of blocking cellular proliferation.

ABSTRACT

The mammalian E2F family of transcription factors plays a crucial role in the regulation of cellular proliferation, apoptosis, and differentiation. Consistent with its biological role in a number of important cellular processes, E2F regulates the expression of genes involved in cell cycle, DNA replication, DNA repair, and mitosis. It has proven difficult, however, to determine the specific roles played by the various known family members in these cellular processes. The work presented here now extends the complexity of this family even further by the identification of a novel E2F family member, which we now term E2F7. Like the expression of the known E2F activators, E2F1, E2F2, and E2F3, the expression of E2F7 is growth-regulated, at least in part, through E2F binding elements on its promoter, and its protein product is localized to the nucleus and associates with DNA E2F recognition sites with high affinity. A number of salient features, however, make this member unique among the E2F family. First, the E2F7 gene encodes a protein that possesses two distinct DNA-binding domains and that lacks a dimerization domain as well as a transcriptional activation and a retinoblastoma-binding domain. In contrast to the E2F activators, E2F7 can block the E2F-dependent activation of a subset of E2F target genes as well as mitigate cellular proliferation of mouse embryo fibroblasts. These findings identify E2F7 as a novel member of the mammalian E2F transcription factor family that has properties of a transcriptional repressor capable of negatively influencing cellular proliferation.