Human E2F-1 reactivates cell cycle progression in ventricular myocytes and represses cardiac gene transcription.

The "pocket" protein- and p300-binding domains of E1A mediate alternative pathways that, independently, provoke S phase reentry in ventricular muscle cells and repress cardiac-specific transcription. In the present study, we utilized recombinant adenovirus to deliver mammalian E2F-1, whose release from pocket proteins may underlie effects of E1A and mitogenic signaling. Like E1A, E2F-1 proved cytotoxic in the absence of E1B. Used along with E1B to avert apoptosis, E2F-1 inhibited the cardiac and skeletal alpha-actin promoters, serum response factor abundance, and sarcomeric actin biosynthesis, while inducing DNA synthesis and proliferating cell nuclear antigen. Image analysis of Feulgen-stained nuclei corroborated a parallel increase in DNA content, with accumulation in G2/M. Thus, E2F-1 suffices for all observed actions of E1A in cardiac myocytes.