Nature Cell Biology4, 859 - 864 (2002)
Published online: 21 October 2002; | doi:10.1038/ncb868
Direct coupling of the cell cycle and cell death machinery by E2F
Zaher Nahle1, 2, Julia Polakoff1, Ramana V. Davuluri1, 4, Mila E. McCurrach1, Matthew D. Jacobson3, Masashi Narita1, Michael Q. Zhang1, Yuri Lazebnik1, Dafna Bar-Sagi3
& Scott W. Lowe1
1
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
2
Department of Physiology and Biophysics, SUNY at Stony Brook, NY 11794, USA
3
Department of Molecular Genetics and Microbiology, SUNY at Stony Brook, NY 11794, USA
4
Current address: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, OH 43210, USA
Correspondence should be addressed to Scott W. Lowe lowe@cshl.edu
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.
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