REGULATION OF THE CYCLIN-E GENE BY TRANSCRIPTION FACTOR E2F1

A variety of results point to the transcription factor E2F as a critic al determinant of the G(1)/S-phase transition during the cell cycle in mammalian cells, serving to activate the transcription of a group of genes that encode proteins necessary for DNA replication. In addition, E2F activity appears to be directly regulated by the action of retino blastoma protein (RE) and RE-related proteins and indirectly regulated through the action of G(1) cyclins and associated kinases. We now sho w that the accumulation of G(1) cyclins is regulated by E2F1, E2F bind ing sites are found in both the cyclin E and cyclin D1 promoters, both promoters are activated by E2F gene products, and at least for cyclin E, the E2F sites contribute to cell cycle-dependent control, Most imp ortant, the endogenous cyclin E gene is activated following expression of the E2F1 product encoded by a recombinant adenovirus vector, These results suggest the involvement of E2F1 and cyclin E in an autoregula tory loop that governs the accumulation of critical activities affecti ng the progression of cells through G(1).