E2F Is Required To Prevent Inappropriate S-Phase Entry of Mammalian Cells

Abstract

E2F is a family of transcription factors that regulates the cell cycle. It is widely accepted that E2F-mediated transactivation of a set of genes is the critical activity that governs cellular progression through G₁ into S phase. In contrast to this hypothesis, we demonstrate that E2F actually suppresses the onset of S phase in two cell types when the cells are arrested by gamma irradiation. Our findings indicate that in these cells, the critical event triggering progression from G₀/G₁ arrest into S phase is the release of E2F-mediated transrepression of cell cycle genes, not transactivation by E2F. Furthermore, our data suggest that E2F-mediated transactivation is not necessary for the G₁/S-phase transition in these cells.

ACKNOWLEDGMENTS

We thank Roger Watson and Peggy Farnham for gifts of the b-myb and DHFR plasmids and L. Carayannopoulos and N. Levy for review of the manuscript.

S.J.W. is supported in part by the NIH and the American Lung Association, and U.W. received support from the Deutscher Akademischer Austauschdienst.

S.H., B.L.C., B.E.D., and U.W. contributed equally to this work.