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

Neuron. 2001 Nov 8;32(3):425-38. doi: 10.1016/s0896-6273(01)00495-0.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Cell Cycle Proteins*
  • Cell Death / drug effects
  • Cell Death / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology
  • DNA-Binding Proteins / metabolism
  • E2F Transcription Factors
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Gene Silencing / drug effects
  • Gene Silencing / physiology
  • Genes, myb / physiology
  • Nerve Growth Factor / administration & dosage
  • Neurons / drug effects
  • Neurons / physiology*
  • PC12 Cells
  • Rats
  • Trans-Activators / metabolism
  • Transcription Factors / physiology*
  • Transcriptional Activation


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • Trans-Activators
  • Transcription Factors
  • Nerve Growth Factor