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Neuron. 2001 Nov 8;32(3):425-38.

Regulation of neuronal survival and death by E2F-dependent gene repression and derepression.

Author information

1
Department of Pathology, Taub Center for Alzheimer's Disease Research, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. dl345@columbia.edu

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.

PMID:
11709154
DOI:
10.1016/s0896-6273(01)00495-0
[Indexed for MEDLINE]
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