Myc requires distinct E2F activities to induce S phase and apoptosis

Previous work has shown that the Myc transcription factor induces transcrip tion of the E2F1, E2F2, and E2F3 genes. Using primary mouse embryo fibrobla sts deleted for individual E2F genes, we now show that Myc-induced S phase and apoptosis requires distinct E2F activities. The ability of Myc to induc e S phase is impaired in the absence of either E2F2 or E2F3 but not E2F1 or E2F4. In contrast, the ability of Myc to induce apoptosis is markedly redu ced in cells deleted for E2F1 but not E2F2 or E2F3. From this data, we prop ose that the induction of specific E2F activities is an essential component in the Myc pathways that control cell proliferation and cell fate decision s.