c-Jun induction is independent of early growth response factor during cerebellar granule neuron apoptosis

Bin Song1, Bo Xie, Chong Wang

  • 1Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Neuroreport
|December 7, 2011
PubMed

Insights

Early Growth Response Factor 1 (Egr-1) does not regulate c-Jun during cerebellar neuron apoptosis. This study found c-Jun induction is independent of Egr-1 signaling in activity-deprived neurons.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Early Growth Response Factor 1 (Egr-1) is implicated in activity deprivation-induced apoptosis of cerebellar granule neurons.
  • c-Jun has been proposed to be a downstream target of the Egr-dependent proapoptotic pathway.

Purpose of the Study:

  • To investigate the relationship between Egr-1 and c-Jun activation during neuronal apoptosis.
  • To determine if Egr-1 signaling is required for c-Jun induction in cerebellar granule neurons undergoing apoptosis.

Main Methods:

  • Utilized dominant-negative Egr mutants and small interfering RNA (siRNA) to suppress Egr activity.
  • Employed transcription inhibitors (mithramycin A, chromomycin A3) that target GC-rich DNA-binding factors.
  • Assessed activation and expression of c-Jun following activity deprivation in cerebellar granule neurons.

Main Results:

  • Suppression of Egr activity or Egr-1 silencing did not inhibit c-Jun activation or expression after activity deprivation.
  • Transcription inhibitors targeting Egr family factors did not attenuate c-Jun activation and expression.
  • These findings indicate Egr-1 is not essential for c-Jun induction in this context.

Conclusions:

  • c-Jun induction is independent of Egr signaling during apoptosis of cerebellar granule neurons induced by activity deprivation.
  • The proposed downstream regulation of c-Jun by Egr-1 in this apoptotic pathway is not supported by these findings.

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