Caspase-dependent apoptosis by ectopic expression of E2F-4

E2F is a family of transcription factors which regulates cell cycle and apo ptosis of mammalian cells. E2F-1-3 localize in the nucleus, and preferentia lly bind pRb, while E2F-4 and 5 have no nuclear localization signal and pre ferentially bind p107/p130. E2F-6 suppresses the transcriptional activity o f other E2F proteins. DP-1 and 2 are heterodimeric partners of each E2F pro tein. Using tetracycline-responsive promoters, here we compared the effects of ectopic expression of E2F-1, DP-I and E2F-4 on cell cycle progression a nd apoptosis in Chinese hamster cell lines, We found that E2F-4, as well as DP-I and E2F-1, induced growth arrest and caspase-dependent apoptosis, E2F -4 did not have a marked effect on cell cycle progression, while E2P-1 indu ced DNA synthesis of resting cells and DP-1 arrested cells in G1, Ectopic e xpression of E2F-4 did not activate E2F-dependent transcription. Our result s suggest that expression of E2F-4 at elevated levels induces growth arrest and apoptosis of mammalian cells through a mechanism distinct from E2F-1 a nd DP-1.