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. 1992 May 11;20(9):2355–2359. doi: 10.1093/nar/20.9.2355

v-Fps-responsiveness in the Egr-1 promoter is mediated by serum response elements.

K Alexandropoulos 1, S A Qureshi 1, M Rim 1, V P Sukhatme 1, D A Foster 1
PMCID: PMC312353  PMID: 1594452

Abstract

Egr-1, a mitogen-responsive transcription factor, is rapidly induced by v-Fps in the absence of protein synthesis. Thus, Egr-1 is a primary response to the protein-tyrosine kinase activity of v-Fps. To determine the v-Fps-responsive elements in the Egr-1 promoter, deletion mutants of the Egr-1 promoter were used in transient expression assays. A v-Fps expression vector was contransfected into NIH 3T3 cells with chloramphenicol acetyl transferase (CAT) gene expression vectors under the control of the Egr-1 promoter or the Egr-1 promoter containing various deletions. Responsiveness to v-Fps was restricted to a region that contained repeated CC(A/T)6GG sequences, known as CArG boxes. CArG boxes form the core of serum response element (SREs). v-Fps-induced Egr-1 promoter activation was lost by sequential removal of four tandemly repeated SREs. This region, containing four SREs, was found to be sufficient for maximal Egr-1 induction by v-Fps when placed upstream from a heterologous promoter. Individual SREs from this region were able to respond to v-Fps, however, the activation of the individual SREs was lower than that observed for the clustered SREs. These data suggest that v-Fps-responsiveness in the Egr-1 promoter is mediated by SREs.

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Selected References

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

  1. Alexandropoulos K., Joseph C. K., Spangler R., Foster D. A. Evidence that a G-protein transduces signals initiated by the protein-tyrosine kinase v-Fps. J Biol Chem. 1991 Aug 25;266(24):15583–15586. [PubMed] [Google Scholar]
  2. Almendral J. M., Sommer D., Macdonald-Bravo H., Burckhardt J., Perera J., Bravo R. Complexity of the early genetic response to growth factors in mouse fibroblasts. Mol Cell Biol. 1988 May;8(5):2140–2148. doi: 10.1128/mcb.8.5.2140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birnbaum M. J., Haspel H. C., Rosen O. M. Transformation of rat fibroblasts by FSV rapidly increases glucose transporter gene transcription. Science. 1987 Mar 20;235(4795):1495–1498. doi: 10.1126/science.3029870. [DOI] [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Christy B., Nathans D. Functional serum response elements upstream of the growth factor-inducible gene zif268. Mol Cell Biol. 1989 Nov;9(11):4889–4895. doi: 10.1128/mcb.9.11.4889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Feldman R. A., Hanafusa T., Hanafusa H. Characterization of protein kinase activity associated with the transforming gene product of Fujinami sarcoma virus. Cell. 1980 Dec;22(3):757–765. doi: 10.1016/0092-8674(80)90552-8. [DOI] [PubMed] [Google Scholar]
  9. Foster D. A., Shibuya M., Hanafusa H. Activation of the transformation potential of the cellular fps gene. Cell. 1985 Aug;42(1):105–115. doi: 10.1016/s0092-8674(85)80106-9. [DOI] [PubMed] [Google Scholar]
  10. Hanafusa T., Mathey-Prevot B., Feldman R. A., Hanafusa H. Mutants of Fujinami sarcoma virus which are temperature sensitive for cellular transformation and protein kinase activity. J Virol. 1981 Apr;38(1):347–355. doi: 10.1128/jvi.38.1.347-355.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hanafusa T., Wang L. H., Anderson S. M., Karess R. E., Hayward W. S., Hanafusa H. Characterization of the transforming gene of Fujinami sarcoma virus. Proc Natl Acad Sci U S A. 1980 May;77(5):3009–3013. doi: 10.1073/pnas.77.5.3009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hatch C. L., Bonner W. M. Direct analysis of RNA in whole cell and cytoplasmic extracts by gel electrophoresis. Anal Biochem. 1987 Apr;162(1):283–290. doi: 10.1016/0003-2697(87)90038-8. [DOI] [PubMed] [Google Scholar]
  13. Herschman H. R. Primary response genes induced by growth factors and tumor promoters. Annu Rev Biochem. 1991;60:281–319. doi: 10.1146/annurev.bi.60.070191.001433. [DOI] [PubMed] [Google Scholar]
  14. Jamal S., Ziff E. Transactivation of c-fos and beta-actin genes by raf as a step in early response to transmembrane signals. Nature. 1990 Mar 29;344(6265):463–466. doi: 10.1038/344463a0. [DOI] [PubMed] [Google Scholar]
  15. Laimins L. A., Gruss P., Pozzatti R., Khoury G. Characterization of enhancer elements in the long terminal repeat of Moloney murine sarcoma virus. J Virol. 1984 Jan;49(1):183–189. doi: 10.1128/jvi.49.1.183-189.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lau L. F., Nathans D. Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1182–1186. doi: 10.1073/pnas.84.5.1182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lim R. W., Varnum B. C., Herschman H. R. Cloning of tetradecanoyl phorbol ester-induced 'primary response' sequences and their expression in density-arrested Swiss 3T3 cells and a TPA non-proliferative variant. Oncogene. 1987;1(3):263–270. [PubMed] [Google Scholar]
  18. Milbrandt J. A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor. Science. 1987 Nov 6;238(4828):797–799. doi: 10.1126/science.3672127. [DOI] [PubMed] [Google Scholar]
  19. Patwardhan S., Gashler A., Siegel M. G., Chang L. C., Joseph L. J., Shows T. B., Le Beau M. M., Sukhatme V. P. EGR3, a novel member of the Egr family of genes encoding immediate-early transcription factors. Oncogene. 1991 Jun;6(6):917–928. [PubMed] [Google Scholar]
  20. Prywes R., Dutta A., Cromlish J. A., Roeder R. G. Phosphorylation of serum response factor, a factor that binds to the serum response element of the c-FOS enhancer. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7206–7210. doi: 10.1073/pnas.85.19.7206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Qureshi S. A., Alexandropoulos K., Joseph C. K., Spangler R., Foster D. A. Cholera toxin induces expression of the immediate-early response gene JE via a cyclic AMP-independent signaling pathway. Mol Cell Biol. 1991 Jan;11(1):102–107. doi: 10.1128/mcb.11.1.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Qureshi S. A., Cao X. M., Sukhatme V. P., Foster D. A. v-Src activates mitogen-responsive transcription factor Egr-1 via serum response elements. J Biol Chem. 1991 Jun 15;266(17):10802–10806. [PubMed] [Google Scholar]
  23. Qureshi S. A., Joseph C. K., Rim M., Maroney A., Foster D. A. v-Src activates both protein kinase C-dependent and independent signaling pathways in murine fibroblasts. Oncogene. 1991 Jun;6(6):995–999. [PubMed] [Google Scholar]
  24. Rauscher F. J., 3rd, Morris J. F., Tournay O. E., Cook D. M., Curran T. Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence. Science. 1990 Nov 30;250(4985):1259–1262. doi: 10.1126/science.2244209. [DOI] [PubMed] [Google Scholar]
  25. Sadowski I., Stone J. C., Pawson T. A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps. Mol Cell Biol. 1986 Dec;6(12):4396–4408. doi: 10.1128/mcb.6.12.4396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Simmons D. L., Levy D. B., Yannoni Y., Erikson R. L. Identification of a phorbol ester-repressible v-src-inducible gene. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1178–1182. doi: 10.1073/pnas.86.4.1178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Spangler R., Joseph C., Qureshi S. A., Berg K. L., Foster D. A. Evidence that v-src and v-fps gene products use a protein kinase C-mediated pathway to induce expression of a transformation-related gene. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7017–7021. doi: 10.1073/pnas.86.18.7017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sukhatme V. P. Early transcriptional events in cell growth: the Egr family. J Am Soc Nephrol. 1990 Dec;1(6):859–866. doi: 10.1681/ASN.V16859. [DOI] [PubMed] [Google Scholar]
  29. Treisman R. Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors. Cell. 1986 Aug 15;46(4):567–574. doi: 10.1016/0092-8674(86)90882-2. [DOI] [PubMed] [Google Scholar]
  30. Treisman R. The SRE: a growth factor responsive transcriptional regulator. Semin Cancer Biol. 1990 Feb;1(1):47–58. [PubMed] [Google Scholar]
  31. Tsai-Morris C. H., Cao X. M., Sukhatme V. P. 5' flanking sequence and genomic structure of Egr-1, a murine mitogen inducible zinc finger encoding gene. Nucleic Acids Res. 1988 Sep 26;16(18):8835–8846. doi: 10.1093/nar/16.18.8835. [DOI] [PMC free article] [PubMed] [Google Scholar]

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