A biological role for Egr-1 in cell survival following ultra-violet irradiation.
The response to ultra-violet (u.v.) irradiation varies among cells, but commonly involves the rapid increase in expression of one or more transcription factors. The specific roles of this increased expression are largely unknown. We show here that in mouse NIH3T3 cells, Egr-1 expression is increased two-fold 10 min after u.v. irradiation, rises to a maximum (eightfold induction) after about 2 h and then declines. The expression of p53 protein is also strongly induced but is maximal between 2 to 4 h before declining. In contrast, the expression of c-Fos, and C-Jun proteins are only slightly affected by u.v. The Egr-1 response is independent of the growth state of the cells but depends on tyrosine kinase and protein kinase C activities. c-Ha-Ras is also involved in the induction of Egr-1 in u.v. irradiated cells. Evidence presented suggests that the mechanism for the response involves oxidative stress rather than DNA damage. We show that Egr-1 functions in the protection of cells against u.v. damage since NIH3T3 cells that constitutively express antisense Egr-1 and consequently cannot produce an Egr-1 response to u.v., grow at a rate 26% less than similarly irradiated parental cells and 36% less than nonirradiated parental cells. This is the second protective role described for Egr-1.
Huang
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La Jolla Cancer Research Foundation, California 92037.
Adamson
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D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000502:physiology / Q000528:radiation effects; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects*; D004249:DNA Damage / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000528:radiation effects; D017874:Immediate-Early Proteins; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology*; D014466:Ultraviolet Rays; D018631:ras Proteins / Q000502:physiology
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D011494:Protein Kinases; D018631:ras Proteins