The Ets transcription factor GABP is required for cell-cycle progression

The transition from cellular quiescence (G0) into S phase is regulated by the mitogenic-activation of D-type cyclins and cyclin-dependent kinases (Cdks), the sequestration of the Cdk inhibitors (CDKIs), p21 and p27, and the hyperphosphorylation of Rb with release of E2F transcription factors(1,2). However, fibroblasts that lack all D-type cyclins can still undergo serum-induced proliferation(3) and key E2F targets are expressed at stable levels despite cyclical Rb-E2F activity(1). Here, we show that serum induces expression of the Ets transcription factor, Gabp alpha, and that its ectopic expression induces quiescent cells to re-enter the cell cycle. Genetic disruption of Gabpa prevents entry into S phase, and selectively reduces expression of genes that are required for DNA synthesis and degradation of CDKIs, yet does not alter expression of D-type cyclins, Cdks, Rb or E2Fs. Thus, GABP is necessary and sufficient for re-entry into the cell cycle and it regulates a pathway that is distinct from that of D-type cyclins and CDKs.