Abstract
Cell cycle machinery controls not only cell growth but also cell survival and death. For example, overexpression of c-Myc or E2F1, which are involved in G1/S transition, causes apoptosis under certain conditions. Furthermore, endogenous E2F1 also participates in apoptosis, as evidenced by the defect of apoptosis in E2F1-deficient mice. Candidate molecules that mediate c-Myc- and E2F1-enhanced apoptosis include p14/p19ARF, ornithine decarboxylase and lactate dehydrogenase-A (for c-Myc) as well as p14/p19ARF, p73, Apaf-1 and caspase-3 (for E2F1). c-Myc also activates the CD95/Fas-FADD-mediated death signal. c-Myc and E2F1 inhibit NF-kappaB activities induced by TNFalpha or reactive oxygen species. Therefore, c-Myc and E2F1 regulate cell growth and death not only by inducing transcription but also by modulating signal transduction pathways.
MeSH terms
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Animals
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Apoptosis / physiology*
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Apoptotic Protease-Activating Factor 1
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Caspase 3
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Caspases / metabolism
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Cell Cycle / physiology
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Cell Cycle Proteins*
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Cell Death / physiology
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Cell Division / physiology*
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Cell Survival / physiology*
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Cyclin-Dependent Kinase Inhibitor p16
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DNA-Binding Proteins / metabolism
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E2F Transcription Factors
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E2F1 Transcription Factor
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Genes, Tumor Suppressor
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Helminth Proteins / metabolism
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Mice
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Muscle Proteins / metabolism
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NF-kappa B / metabolism
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Nuclear Proteins / metabolism
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Protein Interaction Mapping
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Proteins / metabolism
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Proto-Oncogene Proteins c-myc / metabolism*
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S Phase / physiology
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Signal Transduction
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Transcription Factors / metabolism*
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Tumor Protein p73
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Tumor Suppressor Protein p14ARF / metabolism
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Tumor Suppressor Proteins
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fas Receptor / metabolism
Substances
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Apaf1 protein, mouse
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Apoptotic Protease-Activating Factor 1
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Cdkn2a protein, mouse
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p16
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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, mouse
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Helminth Proteins
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Muscle Proteins
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NF-kappa B
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Nuclear Proteins
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Proteins
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Proto-Oncogene Proteins c-myc
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Transcription Factors
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Trp73 protein, mouse
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Tumor Protein p73
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Tumor Suppressor Protein p14ARF
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Tumor Suppressor Proteins
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calponin homolog protein, Schistosoma japonicum
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fas Receptor
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Casp3 protein, mouse
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Caspase 3
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Caspases