E2F and Cell Proliferation: A World Turned Upside Down

This unusual trait-the ability of a single transcription Cambridge, Massachusetts 02142 factor to drive progression all the way through G1-is shared, to this writer's knowledge, with only a single The cottage industry of inactivating genes in the mouse germline is growing by leaps and bounds. However, the other transcription factor, the MYC oncoprotein. Hence, the E2Fs and MYC would appear to sit high in the hierar-making of such mice hardly offers a guaranteed route to interesting results. Often, the phenotypes of the ge-chy that orchestrates the complex succession of events that represents the G1 phase. netically altered mice reinforce already established concepts or are uninformative because of early embryonic Topsy-Turvy Mice The two groups that undertook to inactivate the E2F-1 lethality. On occasion, though, knockout mice do indeed tell us something novel and fully unexpected. Two re-gene in the mouse germline had every right to expect some interesting phenotypes. The fact that there are ports in this issue describe mutant mice with phenotypes that are precisely opposite to those predicted by five E2Fs suggests a measure of functional redundancy, reducing the specter of uninformative, early embryonic conventional wisdom (Field et al., 1996; Yamasaki et al., 1996). lethality. Perhaps, they thought, that the various E2Fs (or at least the three closely allied E2Fs-1,-2 and Ϫ3) Powerful Transcription Factors The E2F transcription factors-the objects of study in would be used in different tissues to differing extents, yielding tissue-specific developmental effects when one these knockout mice-play an especially influential role in advancing mammalian cells through their growth cy-or another E2F gene was inactivated in the germline. The expected outcomes were clear: since E2Fs drive cles. The term " E2F " actually subsumes a group of five closely related proteins (E2F-1 through Ϫ5) and a set cell cycle advance, their absence should yield underdeveloped or even absent tissues. In fact, few if any of of partner proteins, members of the DP family of transcription factors. Heterodimers of E2F and DP proteins these outcomes were observed. The testes in the E2F Ϫ/Ϫ mice were initially normal but then atrophied with ad-assemble in various combinations to form functionally active DNA-binding complexes. These are important for vancing age (Yamasaki et al., 1996; Field et al., 1996). This atrophy would seem to be due to still uncharacter-regulating gene expression in the G1 phase of the cell cycle and perhaps in later phases as well. ized defects in the …