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.
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August 2003
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Research Article|
August 01 2003
The transcription factor early growth response factor-1 (EGR-1) promotes apoptosis of neuroblastoma cells
Miguel PIGNATELLI;
Miguel PIGNATELLI
1
∗Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas-Universidad Autónoma, 28029 Madrid, Spain
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Rosario LUNA-MEDINA;
Rosario LUNA-MEDINA
1
∗Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas-Universidad Autónoma, 28029 Madrid, Spain
2To whom correspondence should be addressed (e-mail aperez@iib.uam.es).
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Arturo PÉREZ-RENDÓN;
Arturo PÉREZ-RENDÓN
∗Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas-Universidad Autónoma, 28029 Madrid, Spain
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Angel SANTOS;
Angel SANTOS
†Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain
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Ana PEREZ-CASTILLO
Ana PEREZ-CASTILLO
2
∗Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas-Universidad Autónoma, 28029 Madrid, Spain
2To whom correspondence should be addressed (e-mail aperez@iib.uam.es).
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Publisher: Portland Press Ltd
Received:
December 11 2002
Revision Received:
May 15 2003
Accepted:
May 19 2003
Accepted Manuscript online:
May 19 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 373 (3): 739–746.
Article history
Received:
December 11 2002
Revision Received:
May 15 2003
Accepted:
May 19 2003
Accepted Manuscript online:
May 19 2003
Citation
Miguel PIGNATELLI, Rosario LUNA-MEDINA, Arturo PÉREZ-RENDÓN, Angel SANTOS, Ana PEREZ-CASTILLO; The transcription factor early growth response factor-1 (EGR-1) promotes apoptosis of neuroblastoma cells. Biochem J 1 August 2003; 373 (3): 739–746. doi: https://doi.org/10.1042/bj20021918
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