C-jun and Egr-1 participate in DNA synthesis and cell survival in response to ionizing radiation exposure.
Exposure of mammalian cells to ionizing radiation results in the induction of the immediate early genes, c-jun and Egr-1, which encode transcription factors implicated in cell growth as well as the cellular response to oxidative stress. We studied the role of these immediate early genes in cell cycle kinetics and cell survival following x-irradiation of clones containing inducible dominant negatives to c-jun and Egr-1. The dominant negative constructs to c-jun (delta 9) and Egr-1 (WT/Egr) prevented x-ray induction of transcription through the AP-1 and Egr binding sites, respectively. Twenty percent of confluent, serum-deprived SQ20B human tumor cells, normal fibroblasts, and fibroblasts from patients with ataxia telangiectasia entered S phase within 5 h of irradiation. Clones containing inducible delta 9 and WT/Egr dominant negative constructs demonstrated attenuation of the percentage of cells exiting G1 phase and reduced survival following irradiation. These data indicate that the dominant negatives to the stress-inducible immediate early genes Egr-1 and c-jun prevent the onset of S phase and reduce the survival of human cells exposed to ionizing radiation.
Hallahan
D E
DE
Department of Radiation and Cellular Oncology, University of Chicago, Illinois 60637, USA.
Dunphy
E
E
Virudachalam
S
S
Sukhatme
V P
VP
Kufe
D W
DW
Weichselbaum
R R
RR
D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects*; D003001:Cloning, Molecular; D004261:DNA Replication / Q000528:radiation effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051766:Early Growth Response Protein 1; D017781:Genes, Immediate-Early / Q000528:radiation effects*; D016758:Genes, jun / Q000528:radiation effects*; D006801:Humans; D017874:Immediate-Early Proteins; D007700:Kinetics; D007822:Laryngeal Neoplasms; D011519:Proto-Oncogenes / Q000528:radiation effects*; D013431:Sulfates / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D014965:X-Rays; D017967:Zinc Compounds / Q000494:pharmacology; D019287:Zinc Sulfate
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D013431:Sulfates; D014157:Transcription Factors; D017967:Zinc Compounds; D019287:Zinc Sulfate