The transcription factor early growth response factor-1 (EGR-1) promotes apoptosis of neuroblastoma cells

Biochem J. 2003 Aug 1;373(Pt 3):739-46. doi: 10.1042/BJ20021918.

Abstract

Early growth response factor-1 (EGR-1) is an immediate early gene, which is rapidly activated in quiescent cells by mitogens or in postmitotic neurons after depolarization. EGR-1 has been involved in diverse biological functions such as cell growth, differentiation and apoptosis. Here we report that enforced expression of the EGR-1 gene induces apoptosis, as determined by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end labelling (TUNEL) analysis, in murine Neuro2A cells. In accordance with this role of EGR-1 in cell death, antisense oligonucleotides increase cell viability in cells cultured in the absence of serum. This apoptotic activity of the EGR-1 appears to be mediated by p73, a member of the p53 family of proteins, since an increase in the amount of p73 is observed in clones stably expressing the EGR-1 protein. We also observed an increase in the transcriptional activity of the mdm2 promoter in cells overexpressing EGR-1, which is paralleled by a marked decrease in the levels of p53 protein, therefore excluding a role of this protein in mediating EGR-1-induced apoptosis. Our results suggest that EGR-1 is an important factor involved in neuronal apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Base Sequence
  • Cell Survival / physiology
  • DNA-Binding Proteins / physiology*
  • Early Growth Response Protein 1
  • Immediate-Early Proteins*
  • Mice
  • Neuroblastoma / pathology*
  • Oligonucleotides, Antisense
  • Transcription Factors / physiology*
  • Tumor Suppressor Protein p53 / physiology

Substances

  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Immediate-Early Proteins
  • Oligonucleotides, Antisense
  • Transcription Factors
  • Tumor Suppressor Protein p53