The transcription factor early growth response factor-1 (EGR-1) promotes apoptosis of neuroblastoma cells.
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.
Pignatelli
Miguel
M
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas-Universidad Autónoma, 28029 Madrid, Spain.
Luna-Medina
Rosario
R
Pérez-Rendón
Arturo
A
Santos
Angel
A
Perez-Castillo
Ana
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology*; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53