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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenovirus E1A Proteins / metabolism
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Animals
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Apoptosis*
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Blotting, Northern
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Caspases / genetics
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Caspases / metabolism
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Cell Cycle
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Cell Cycle Proteins*
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Cell Line, Tumor
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CpG Islands
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Cytochromes c / metabolism
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DNA-Binding Proteins*
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E2F Transcription Factors
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E2F1 Transcription Factor
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Fibroblasts / metabolism
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Humans
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Luciferases / metabolism
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Mice
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Models, Biological
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Models, Genetic
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Promoter Regions, Genetic
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RNA / chemistry
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Retinoblastoma Protein / metabolism
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Time Factors
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Transcription Factors / chemistry*
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Transcription Factors / physiology*
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Transcription, Genetic
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Tumor Suppressor Protein p53 / metabolism
Substances
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Adenovirus E1A Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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E2F Transcription Factors
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E2F1 Transcription Factor
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E2F1 protein, human
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E2f1 protein, mouse
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Retinoblastoma Protein
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Transcription Factors
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Tumor Suppressor Protein p53
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RNA
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Cytochromes c
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Luciferases
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Caspases