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Nature Cell Biology 4, 859–864 (1 November 2002) | doi:10.1038/ncb868

Direct coupling of the cell cycle and cell death machinery by E2F

Zaher Nahle , Julia Polakoff , Ramana V. Davuluri , Mila E. McCurrach , Matthew D. Jacobson , Masashi Narita , Michael Q. Zhang , Yuri Lazebnik , Dafna Bar-Sagi & Scott W. Lowe

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.