The transcription factor early growth response factor-1 (EGR-1) promotes apoptosis of neuroblastoma cells
Open Access
- 1 August 2003
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 373 (3), 739-746
- https://doi.org/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.Keywords
This publication has 59 references indexed in Scilit:
- Regulation of life and death by the zinc finger transcription factor Egr‐1Journal of Cellular Physiology, 2002
- A System for Stable Expression of Short Interfering RNAs in Mammalian CellsScience, 2002
- p73The International Journal of Biochemistry & Cell Biology, 2001
- c-Abl: activation and nuclear targetsCell Death & Differentiation, 2000
- Regulation of p53 stability by Mdm2Nature, 1997
- Mdm2 promotes the rapid degradation of p53Nature, 1997
- EGR-1 Induction Is Required for Maximal Radiosensitivity in A375-C6 Melanoma CellsPublished by Elsevier BV ,1996
- An S1 nuclease-sensitive homopurine/homopyrimidine domain in the PDGF A-chain promoter contains a novel binding site for the growth factor-inducible protein EGR-1Biochemical and Biophysical Research Communications, 1992
- Neurotrophic factors: From physiology to pharmacology?Pharmacological Research, 1992
- Thyroid Hormones and Brain DevelopmentAnnual Review of Physiology, 1987