Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1996 Jun 1;316(Pt 2):381–383. doi: 10.1042/bj3160381

Functional activation of the egr-1 (early growth response-1) gene by hydrogen peroxide.

K Nose 1, M Ohba 1
PMCID: PMC1217360  PMID: 8687376

Abstract

The redox-based regulation of gene expression is one of the fundamental mechanisms of cellular functions, and hydrogen peroxide seems to act as an intracellular second messenger of signal transduction of cytokines. Hydrogen peroxide at non-toxic doses induced the accumulation of mRNA for the early growth response-1 (egr-1) gene in mouse osteoblastic cells. The Egr-1 protein is a transcription factor that binds the GCGGGGGCG sequence and contains a zinc-finger structure that is essential for DNA binding. Egr-1 protein is sensitive to oxidative stress and loses specific DNA-binding activity when exposed to high levels of oxidative stress. Incubating cells with hydrogen peroxide at about 50 microM, however, increased the accumulation of Egr-1 protein, and the Egr-1 product seemed to be functional, judging by its binding activity to the GCGGGGGCG sequence and its ability to activate the chloramphenicol acetyltransferase reporter gene under the control of the human thymidine kinase enhancer containing the Egr-1 binding sequence. It was reported that the activity of Egr-1 protein as a transcription factor was negatively regulated by active oxygens. However, with appropriate concentrations of active oxygen, its capacity to bind a specific DNA sequence and to enhance the transcriptional activity of target genes is thought to be elevated.

Full Text

The Full Text of this article is available as a PDF (228.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abate C., Patel L., Rauscher F. J., 3rd, Curran T. Redox regulation of fos and jun DNA-binding activity in vitro. Science. 1990 Sep 7;249(4973):1157–1161. doi: 10.1126/science.2118682. [DOI] [PubMed] [Google Scholar]
  2. Bauskin A. R., Alkalay I., Ben-Neriah Y. Redox regulation of a protein tyrosine kinase in the endoplasmic reticulum. Cell. 1991 Aug 23;66(4):685–696. doi: 10.1016/0092-8674(91)90114-e. [DOI] [PubMed] [Google Scholar]
  3. Cao X. M., Koski R. A., Gashler A., McKiernan M., Morris C. F., Gaffney R., Hay R. V., Sukhatme V. P. Identification and characterization of the Egr-1 gene product, a DNA-binding zinc finger protein induced by differentiation and growth signals. Mol Cell Biol. 1990 May;10(5):1931–1939. doi: 10.1128/mcb.10.5.1931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Christy B., Nathans D. DNA binding site of the growth factor-inducible protein Zif268. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8737–8741. doi: 10.1073/pnas.86.22.8737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Esposito F., Agosti V., Morrone G., Morra F., Cuomo C., Russo T., Venuta S., Cimino F. Inhibition of the differentiation of human myeloid cell lines by redox changes induced through glutathione depletion. Biochem J. 1994 Aug 1;301(Pt 3):649–653. doi: 10.1042/bj3010649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  9. Guy G. R., Cairns J., Ng S. B., Tan Y. H. Inactivation of a redox-sensitive protein phosphatase during the early events of tumor necrosis factor/interleukin-1 signal transduction. J Biol Chem. 1993 Jan 25;268(3):2141–2148. [PubMed] [Google Scholar]
  10. Hentze M. W., Rouault T. A., Harford J. B., Klausner R. D. Oxidation-reduction and the molecular mechanism of a regulatory RNA-protein interaction. Science. 1989 Apr 21;244(4902):357–359. doi: 10.1126/science.2711187. [DOI] [PubMed] [Google Scholar]
  11. Huang R. P., Adamson E. D. Characterization of the DNA-binding properties of the early growth response-1 (Egr-1) transcription factor: evidence for modulation by a redox mechanism. DNA Cell Biol. 1993 Apr;12(3):265–273. doi: 10.1089/dna.1993.12.265. [DOI] [PubMed] [Google Scholar]
  12. Kurihara N., Ishizuka S., Kiyoki M., Haketa Y., Ikeda K., Kumegawa M. Effects of 1,25-dihydroxyvitamin D3 on osteoblastic MC3T3-E1 cells. Endocrinology. 1986 Mar;118(3):940–947. doi: 10.1210/endo-118-3-940. [DOI] [PubMed] [Google Scholar]
  13. Meier B., Radeke H. H., Selle S., Younes M., Sies H., Resch K., Habermehl G. G. Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-alpha. Biochem J. 1989 Oct 15;263(2):539–545. doi: 10.1042/bj2630539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Meister A. Selective modification of glutathione metabolism. Science. 1983 Apr 29;220(4596):472–477. doi: 10.1126/science.6836290. [DOI] [PubMed] [Google Scholar]
  15. Meyer M., Schreck R., Baeuerle P. A. H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor. EMBO J. 1993 May;12(5):2005–2015. doi: 10.1002/j.1460-2075.1993.tb05850.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Molnar G., Crozat A., Pardee A. B. The immediate-early gene Egr-1 regulates the activity of the thymidine kinase promoter at the G0-to-G1 transition of the cell cycle. Mol Cell Biol. 1994 Aug;14(8):5242–5248. doi: 10.1128/mcb.14.8.5242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Morris J. F., Madden S. L., Tournay O. E., Cook D. M., Sukhatme V. P., Rauscher F. J., 3rd Characterization of the zinc finger protein encoded by the WT1 Wilms' tumor locus. Oncogene. 1991 Dec;6(12):2339–2348. [PubMed] [Google Scholar]
  18. Nguyen H. Q., Hoffman-Liebermann B., Liebermann D. A. The zinc finger transcription factor Egr-1 is essential for and restricts differentiation along the macrophage lineage. Cell. 1993 Jan 29;72(2):197–209. doi: 10.1016/0092-8674(93)90660-i. [DOI] [PubMed] [Google Scholar]
  19. Nose K., Shibanuma M., Kikuchi K., Kageyama H., Sakiyama S., Kuroki T. Transcriptional activation of early-response genes by hydrogen peroxide in a mouse osteoblastic cell line. Eur J Biochem. 1991 Oct 1;201(1):99–106. doi: 10.1111/j.1432-1033.1991.tb16261.x. [DOI] [PubMed] [Google Scholar]
  20. Ohba M., Shibanuma M., Kuroki T., Nose K. Production of hydrogen peroxide by transforming growth factor-beta 1 and its involvement in induction of egr-1 in mouse osteoblastic cells. J Cell Biol. 1994 Aug;126(4):1079–1088. doi: 10.1083/jcb.126.4.1079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schreck R., Baeuerle P. A. A role for oxygen radicals as second messengers. Trends Cell Biol. 1991 Aug;1(2-3):39–42. doi: 10.1016/0962-8924(91)90072-h. [DOI] [PubMed] [Google Scholar]
  22. Schreck R., Rieber P., Baeuerle P. A. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J. 1991 Aug;10(8):2247–2258. doi: 10.1002/j.1460-2075.1991.tb07761.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shibanuma M., Kuroki T., Nose K. Inhibition by N-acetyl-L-cysteine of interleukin-6 mRNA induction and activation of NF kappa B by tumor necrosis factor alpha in a mouse fibroblastic cell line, Balb/3T3. FEBS Lett. 1994 Oct 10;353(1):62–66. doi: 10.1016/0014-5793(94)01014-5. [DOI] [PubMed] [Google Scholar]
  24. Sundaresan M., Yu Z. X., Ferrans V. J., Irani K., Finkel T. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science. 1995 Oct 13;270(5234):296–299. doi: 10.1126/science.270.5234.296. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES