Unrestrained E2F activity forces S phase entry and promotes apoptosis through p53-dependent and -independent mechanisms. Here, we show that deregulation of E2F by adenovirus E1A, loss of Rb or enforced E2F-1 expression results in the accumulation of caspase proenzymes through a direct transcriptional mechanism. Increased caspase levels seem to potentiate cell death in the presence of p53-generated signals that trigger caspase activation. Our results demonstrate that mitogenic oncogenes engage a tumour suppressor network that functions at multiple levels to efficiently induce cell death. The data also underscore how cell cycle progression can be coupled to the apoptotic machinery.
ASJC Scopus subject areas
- Cell Biology