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. 1988 May;8(5):2063–2069. doi: 10.1128/mcb.8.5.2063

fra-1: a serum-inducible, cellular immediate-early gene that encodes a fos-related antigen.

D R Cohen 1, T Curran 1
PMCID: PMC363385  PMID: 3133553

Abstract

A set of proteins antigenically related to the c-fos protein (Fos) are induced by serum in fibroblasts. To isolate cDNA clones of genes encoding such proteins, a lambda gt11 expression cDNA library constructed from serum-stimulated rat fibroblasts was screened with antibodies raised against a hydrophilic region (amino acids 127 to 152) of Fos. One of the positive clones identified, termed fra-1 (Fos-related antigen) was characterized. It encoded a protein that shared several regions of extensive amino acid homology with Fos (including the region that showed similarity to both the yeast GCN4 regulatory protein and the protein encoded by the jun oncogene), although its nucleotide sequence was considerably diverged from that of the c-fos gene. Only a subset of the agents and conditions that activated c-fos also induced fra-1. Induction of fra-1 expression following serum stimulation was delayed compared with that of c-fos. However, like c-fos, fra-1 was induced rapidly by serum in the presence of protein synthesis inhibitors. Thus, a family of Fos-related, inducible genes are involved in the cellular immediate-early transcriptional response to extracellular stimuli.

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Selected References

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  1. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  2. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bohmann D., Bos T. J., Admon A., Nishimura T., Vogt P. K., Tjian R. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science. 1987 Dec 4;238(4832):1386–1392. doi: 10.1126/science.2825349. [DOI] [PubMed] [Google Scholar]
  4. Cochran B. H., Reffel A. C., Stiles C. D. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell. 1983 Jul;33(3):939–947. doi: 10.1016/0092-8674(83)90037-5. [DOI] [PubMed] [Google Scholar]
  5. Cochran B. H., Zullo J., Verma I. M., Stiles C. D. Expression of the c-fos gene and of an fos-related gene is stimulated by platelet-derived growth factor. Science. 1984 Nov 30;226(4678):1080–1082. doi: 10.1126/science.6093261. [DOI] [PubMed] [Google Scholar]
  6. Curran T., Gordon M. B., Rubino K. L., Sambucetti L. C. Isolation and characterization of the c-fos(rat) cDNA and analysis of post-translational modification in vitro. Oncogene. 1987;2(1):79–84. [PubMed] [Google Scholar]
  7. Curran T., Miller A. D., Zokas L., Verma I. M. Viral and cellular fos proteins: a comparative analysis. Cell. 1984 Feb;36(2):259–268. doi: 10.1016/0092-8674(84)90219-8. [DOI] [PubMed] [Google Scholar]
  8. Curran T., Morgan J. I. Barium modulates c-fos expression and post-translational modification. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8521–8524. doi: 10.1073/pnas.83.22.8521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Curran T., Morgan J. I. Superinduction of c-fos by nerve growth factor in the presence of peripherally active benzodiazepines. Science. 1985 Sep 20;229(4719):1265–1268. doi: 10.1126/science.4035354. [DOI] [PubMed] [Google Scholar]
  10. Curran T., Peters G., Van Beveren C., Teich N. M., Verma I. M. FBJ murine osteosarcoma virus: identification and molecular cloning of biologically active proviral DNA. J Virol. 1982 Nov;44(2):674–682. doi: 10.1128/jvi.44.2.674-682.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Curran T., Teich N. M. Candidate product of the FBJ murine osteosarcoma virus oncogene: characterization of a 55,000-dalton phosphoprotein. J Virol. 1982 Apr;42(1):114–122. doi: 10.1128/jvi.42.1.114-122.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Curran T., Van Beveren C., Verma I. M. Viral and cellular fos proteins are complexed with a 39,000-dalton cellular protein. Mol Cell Biol. 1985 Jan;5(1):167–172. doi: 10.1128/mcb.5.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Curran T., Verma I. M. FBR murine osteosarcoma virus. I. Molecular analysis and characterization of a 75,000-Da gag-fos fusion product. Virology. 1984 May;135(1):218–228. doi: 10.1016/0042-6822(84)90132-6. [DOI] [PubMed] [Google Scholar]
  14. Distel R. J., Ro H. S., Rosen B. S., Groves D. L., Spiegelman B. M. Nucleoprotein complexes that regulate gene expression in adipocyte differentiation: direct participation of c-fos. Cell. 1987 Jun 19;49(6):835–844. doi: 10.1016/0092-8674(87)90621-0. [DOI] [PubMed] [Google Scholar]
  15. Franza B. R., Jr, Sambucetti L. C., Cohen D. R., Curran T. Analysis of Fos protein complexes and Fos-related antigens by high-resolution two-dimensional gel electrophoresis. Oncogene. 1987 May;1(2):213–221. [PubMed] [Google Scholar]
  16. Greenberg M. E., Hermanowski A. L., Ziff E. B. Effect of protein synthesis inhibitors on growth factor activation of c-fos, c-myc, and actin gene transcription. Mol Cell Biol. 1986 Apr;6(4):1050–1057. doi: 10.1128/mcb.6.4.1050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
  18. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  19. Helms C., Graham M. Y., Dutchik J. E., Olson M. V. A new method for purifying lambda DNA from phage lysates. DNA. 1985 Feb;4(1):39–49. doi: 10.1089/dna.1985.4.39. [DOI] [PubMed] [Google Scholar]
  20. Hill D. E., Hope I. A., Macke J. P., Struhl K. Saturation mutagenesis of the yeast his3 regulatory site: requirements for transcriptional induction and for binding by GCN4 activator protein. Science. 1986 Oct 24;234(4775):451–457. doi: 10.1126/science.3532321. [DOI] [PubMed] [Google Scholar]
  21. Hinnebusch A. G., Lucchini G., Fink G. R. A synthetic HIS4 regulatory element confers general amino acid control on the cytochrome c gene (CYC1) of yeast. Proc Natl Acad Sci U S A. 1985 Jan;82(2):498–502. doi: 10.1073/pnas.82.2.498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hope I. A., Struhl K. Functional dissection of a eukaryotic transcriptional activator protein, GCN4 of yeast. Cell. 1986 Sep 12;46(6):885–894. doi: 10.1016/0092-8674(86)90070-x. [DOI] [PubMed] [Google Scholar]
  23. Hope I. A., Struhl K. GCN4 protein, synthesized in vitro, binds HIS3 regulatory sequences: implications for general control of amino acid biosynthetic genes in yeast. Cell. 1985 Nov;43(1):177–188. doi: 10.1016/0092-8674(85)90022-4. [DOI] [PubMed] [Google Scholar]
  24. Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jenuwein T., Müller R. Structure-function analysis of fos protein: a single amino acid change activates the immortalizing potential of v-fos. Cell. 1987 Feb 27;48(4):647–657. doi: 10.1016/0092-8674(87)90243-1. [DOI] [PubMed] [Google Scholar]
  26. Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
  27. Kruijer W., Cooper J. A., Hunter T., Verma I. M. Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature. 1984 Dec 20;312(5996):711–716. doi: 10.1038/312711a0. [DOI] [PubMed] [Google Scholar]
  28. Kujubu D. A., Lim R. W., Varnum B. C., Herschman H. R. Induction of transiently expressed genes in PC-12 pheochromocytoma cells. Oncogene. 1987;1(3):257–262. [PubMed] [Google Scholar]
  29. 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]
  30. Lau L. F., Nathans D. Identification of a set of genes expressed during the G0/G1 transition of cultured mouse cells. EMBO J. 1985 Dec 1;4(12):3145–3151. doi: 10.1002/j.1460-2075.1985.tb04057.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Morgan J. I., Cohen D. R., Hempstead J. L., Curran T. Mapping patterns of c-fos expression in the central nervous system after seizure. Science. 1987 Jul 10;237(4811):192–197. doi: 10.1126/science.3037702. [DOI] [PubMed] [Google Scholar]
  33. Müller R., Bravo R., Burckhardt J., Curran T. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature. 1984 Dec 20;312(5996):716–720. doi: 10.1038/312716a0. [DOI] [PubMed] [Google Scholar]
  34. Pledger W. J., Stiles C. D., Antoniades H. N., Scher C. D. Induction of DNA synthesis in BALB/c 3T3 cells by serum components: reevaluation of the commitment process. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4481–4485. doi: 10.1073/pnas.74.10.4481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Quade K. Transformation of mammalian cells by avian myelocytomatosis virus and avian erythroblastosis virus. Virology. 1979 Oct 30;98(2):461–465. doi: 10.1016/0042-6822(79)90569-5. [DOI] [PubMed] [Google Scholar]
  36. Rakusanova T., Ben-Porat T., Himeno M., Kaplan A. S. Early functions of the genome of herpesvirus. I. Characterization of the RNA synthesized in cycloheximide-treated, infected cells. Virology. 1971 Dec;46(3):877–889. doi: 10.1016/0042-6822(71)90088-2. [DOI] [PubMed] [Google Scholar]
  37. Renz M., Verrier B., Kurz C., Müller R. Chromatin association and DNA binding properties of the c-fos proto-oncogene product. Nucleic Acids Res. 1987 Jan 12;15(1):277–292. doi: 10.1093/nar/15.1.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Salser W., Bolle A., Epstein R. Transcription during bacteriophage T4 development: a demonstration that distinct subclasses of the "early" RNA appear at different times and that some are "turned off" at late times. J Mol Biol. 1970 Apr 28;49(2):271–295. doi: 10.1016/0022-2836(70)90246-9. [DOI] [PubMed] [Google Scholar]
  39. Sambucetti L. C., Curran T. The Fos protein complex is associated with DNA in isolated nuclei and binds to DNA cellulose. Science. 1986 Dec 12;234(4782):1417–1419. doi: 10.1126/science.3491427. [DOI] [PubMed] [Google Scholar]
  40. Sambucetti L. C., Schaber M., Kramer R., Crowl R., Curran T. The fos gene product undergoes extensive post-translational modification in eukaryotic but not in prokaryotic cells. Gene. 1986;43(1-2):69–77. doi: 10.1016/0378-1119(86)90009-0. [DOI] [PubMed] [Google Scholar]
  41. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  42. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  43. Struhl K. The DNA-binding domains of the jun oncoprotein and the yeast GCN4 transcriptional activator protein are functionally homologous. Cell. 1987 Sep 11;50(6):841–846. doi: 10.1016/0092-8674(87)90511-3. [DOI] [PubMed] [Google Scholar]
  44. Sukhatme V. P., Kartha S., Toback F. G., Taub R., Hoover R. G., Tsai-Morris C. H. A novel early growth response gene rapidly induced by fibroblast, epithelial cell and lymphocyte mitogens. Oncogene Res. 1987 Sep-Oct;1(4):343–355. [PubMed] [Google Scholar]
  45. Vogt P. K., Bos T. J., Doolittle R. F. Homology between the DNA-binding domain of the GCN4 regulatory protein of yeast and the carboxyl-terminal region of a protein coded for by the oncogene jun. Proc Natl Acad Sci U S A. 1987 May;84(10):3316–3319. doi: 10.1073/pnas.84.10.3316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Yamamoto K. R., Alberts B. M. Steroid receptors: elements for modulation of eukaryotic transcription. Annu Rev Biochem. 1976;45:721–746. doi: 10.1146/annurev.bi.45.070176.003445. [DOI] [PubMed] [Google Scholar]
  47. Young R. A., Davis R. W. Efficient isolation of genes by using antibody probes. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1194–1198. doi: 10.1073/pnas.80.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Young R. A., Davis R. W. Yeast RNA polymerase II genes: isolation with antibody probes. Science. 1983 Nov 18;222(4625):778–782. doi: 10.1126/science.6356359. [DOI] [PubMed] [Google Scholar]

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