Abstract
Neuronal death induced by a variety of means requires participation of the E2F family of transcription factors. Here, we show that E2F acts as a gene silencer in neurons and that repression of E2F-responsive genes is required for neuronal survival. Moreover, neuronal death evoked by DNA damaging agents or trophic factor withdrawal is characterized by derepression of E2F-responsive genes. Such derepression, rather than direct E2F-promoted gene activation, is required for death. Among the genes that are derepressed in neurons subjected to DNA damage or trophic factor withdrawal are the transcription factors B- and C-myb. Overexpression of B- and C-myb is sufficient to evoke neuronal death. These findings support a model in which E2F-dependent gene repression and derepression play pivotal roles in neuronal survival and death, respectively.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / genetics*
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Cell Cycle Proteins*
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Cell Death / drug effects
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Cell Death / genetics
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Cell Survival / drug effects
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Cell Survival / genetics
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Cerebral Cortex / cytology
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Cerebral Cortex / drug effects
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Cerebral Cortex / physiology
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DNA-Binding Proteins / metabolism
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E2F Transcription Factors
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Gene Silencing / drug effects
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Gene Silencing / physiology
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Genes, myb / physiology
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Nerve Growth Factor / administration & dosage
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Neurons / drug effects
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Neurons / physiology*
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PC12 Cells
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Rats
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Trans-Activators / metabolism
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Transcription Factors / physiology*
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Transcriptional Activation
Substances
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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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Trans-Activators
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Transcription Factors
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Nerve Growth Factor