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

Abstract:: 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.

Authors:: Z Nahle, J Polakoff, RV Davuluri, ME McCurrach, MD Jacobson, M Narita, MQ Zhang, Y Lazebnik, D Bar-Sagi, SW Lowe

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