Abstract
E2F transcription factors are key targets of the retinoblastoma (Rb) tumor suppressor. Despite extensive studies, the in vivo consequences of disrupting the interaction between Rb and an individual E2F are not clear. Here, we report an E2F mutation that interfered with binding to Rb family proteins without significantly affecting protein level or transactivation function. Characterization of mouse embryonic fibroblasts with this Rb-independent E2F3(LQ) mutation revealed that disrupting the Rb and E2F3 interaction increased cell proliferation, allowed cells to accumulate to higher density, and significantly altered expression of genes involved in metabolism, inflammation, immunity, and response to stress. These results suggest that the Rb-independent E2F(LQ) mutations might provide useful tools to investigate the in vivo consequences of disrupting the interactions between Rb and E2F.