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    Nat Cell Biol. 2002 Nov;4(11):859-64.

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

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

    Source

    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

    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.

    PMID:
    12389032
    [PubMed - indexed for MEDLINE]

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