AUTOREGULATORY CONTROL OF E2F1 EXPRESSION IN RESPONSE TO POSITIVE ANDNEGATIVE REGULATORS OF CELL-CYCLE PROGRESSION

Both positive and negative signals govern the progression of cells fro m G(1) into S phase, and a variety of data implicate the E2F transcrip tion factor as a target for the action of one class of negative regula tors, the Rb family of growth suppressors. We now find that the E2F1 g ene, which encodes one of the components of E2F activity, is subject t o autoregulatory control during progression from G(0) to S phase and t hat this primarily reflects a negative control in G(0) and early G(1), a time when the majority of E2F activity exits as a complex with Rb f amily members. In addition, we find that deregulated expression of G(1 ), cyclins in quiescent cells stimulates the E2F1 promoter and that th is is augmented by coexpression of cyclin-dependent kinases in an E2F- dependent manner. We conclude that the E2F1 gene is a downstream targe t for G(1) cyclin dependent kinase activity, most likely as a conseque nce of phosphorylation of Rb family members, and that the autoregulati on of E2F1 transcription may provide a sensitive switch for regulating the accumulation of E2F activity during the transition from G(1) to S phase.