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. 1992 Oct;12(10):4472–4477. doi: 10.1128/mcb.12.10.4472

Mapping of epidermal growth factor-, serum-, and phorbol ester-responsive sequence elements in the c-jun promoter.

T H Han 1, W W Lamph 1, R Prywes 1
PMCID: PMC360372  PMID: 1406636

Abstract

Expression of the nuclear proto-oncogene c-jun is rapidly and transiently induced by many growth factors, serum, and tumor promoters. The sequence elements in the c-jun promoter involved in serum or growth factor induction have not been identified. The c-jun promoter region between -117 and -72 contains binding sites for the transcription factors Sp1, CTF, and AP-1. An additional sequence element has been noted at position -59. This A+T-rich sequence, formerly proposed as a TFIID-binding site, conforms to the consensus binding sequence of a recently identified factor, RSRF (related to serum response factor). In this study, we mapped the sequences in the c-jun promoter responsible for epidermal growth factor (EGF), serum, and 12-O-tetradecanoylphorbol-13-acetate (TPA) induction by deletion and point mutational analysis. We found that the c-jun RSRF site is an important element for EGF and serum induction of the promoter and that there are several factors in HeLa nuclear extracts which specifically bind to this site. The RSRF site was also sufficient for EGF, serum, and TPA induction when assayed on a heterologous promoter. The c-jun AP-1 site was not required for EGF, serum, or TPA induction but was sufficient to mediate a weak response to these agents when assayed on a heterologous promoter. Double mutation of the RSRF and AP-1 sites suggests that there is an additional TPA-responsive element between -80 and +150 in the c-jun promoter.

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Selected References

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

  1. Angel P., Hattori K., Smeal T., Karin M. The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1. Cell. 1988 Dec 2;55(5):875–885. doi: 10.1016/0092-8674(88)90143-2. [DOI] [PubMed] [Google Scholar]
  2. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  3. Brenner D. A., O'Hara M., Angel P., Chojkier M., Karin M. Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha. Nature. 1989 Feb 16;337(6208):661–663. doi: 10.1038/337661a0. [DOI] [PubMed] [Google Scholar]
  4. Chiu R., Imagawa M., Imbra R. J., Bockoven J. R., Karin M. Multiple cis- and trans-acting elements mediate the transcriptional response to phorbol esters. Nature. 1987 Oct 15;329(6140):648–651. doi: 10.1038/329648a0. [DOI] [PubMed] [Google Scholar]
  5. Fisch T. M., Prywes R., Roeder R. G. c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore. Mol Cell Biol. 1987 Oct;7(10):3490–3502. doi: 10.1128/mcb.7.10.3490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gilman M. Z., Wilson R. N., Weinberg R. A. Multiple protein-binding sites in the 5'-flanking region regulate c-fos expression. Mol Cell Biol. 1986 Dec;6(12):4305–4316. doi: 10.1128/mcb.6.12.4305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hattori K., Angel P., Le Beau M. M., Karin M. Structure and chromosomal localization of the functional intronless human JUN protooncogene. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9148–9152. doi: 10.1073/pnas.85.23.9148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Kitabayashi I., Kawakami Z., Chiu R., Ozawa K., Matsuoka T., Toyoshima S., Umesono K., Evans R. M., Gachelin G., Yokoyama K. Transcriptional regulation of the c-jun gene by retinoic acid and E1A during differentiation of F9 cells. EMBO J. 1992 Jan;11(1):167–175. doi: 10.1002/j.1460-2075.1992.tb05039.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kovary K., Bravo R. The jun and fos protein families are both required for cell cycle progression in fibroblasts. Mol Cell Biol. 1991 Sep;11(9):4466–4472. doi: 10.1128/mcb.11.9.4466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lamph W. W., Dwarki V. J., Ofir R., Montminy M., Verma I. M. Negative and positive regulation by transcription factor cAMP response element-binding protein is modulated by phosphorylation. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4320–4324. doi: 10.1073/pnas.87.11.4320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lamph W. W., Wamsley P., Sassone-Corsi P., Verma I. M. Induction of proto-oncogene JUN/AP-1 by serum and TPA. Nature. 1988 Aug 18;334(6183):629–631. doi: 10.1038/334629a0. [DOI] [PubMed] [Google Scholar]
  13. Lee W., Mitchell P., Tjian R. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell. 1987 Jun 19;49(6):741–752. doi: 10.1016/0092-8674(87)90612-x. [DOI] [PubMed] [Google Scholar]
  14. Lieberman P. M., Berk A. J. The Zta trans-activator protein stabilizes TFIID association with promoter DNA by direct protein-protein interaction. Genes Dev. 1991 Dec;5(12B):2441–2454. doi: 10.1101/gad.5.12b.2441. [DOI] [PubMed] [Google Scholar]
  15. Manak J. R., de Bisschop N., Kris R. M., Prywes R. Casein kinase II enhances the DNA binding activity of serum response factor. Genes Dev. 1990 Jun;4(6):955–967. doi: 10.1101/gad.4.6.955. [DOI] [PubMed] [Google Scholar]
  16. Norman C., Runswick M., Pollock R., Treisman R. Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell. 1988 Dec 23;55(6):989–1003. doi: 10.1016/0092-8674(88)90244-9. [DOI] [PubMed] [Google Scholar]
  17. Pollock R., Treisman R. Human SRF-related proteins: DNA-binding properties and potential regulatory targets. Genes Dev. 1991 Dec;5(12A):2327–2341. doi: 10.1101/gad.5.12a.2327. [DOI] [PubMed] [Google Scholar]
  18. Prywes R., Fisch T. M., Roeder R. G. Transcriptional regulation of c-fos. Cold Spring Harb Symp Quant Biol. 1988;53(Pt 2):739–748. doi: 10.1101/sqb.1988.053.01.084. [DOI] [PubMed] [Google Scholar]
  19. Prywes R., Roeder R. G. Inducible binding of a factor to the c-fos enhancer. Cell. 1986 Dec 5;47(5):777–784. doi: 10.1016/0092-8674(86)90520-9. [DOI] [PubMed] [Google Scholar]
  20. Prywes R., Roeder R. G. Purification of the c-fos enhancer-binding protein. Mol Cell Biol. 1987 Oct;7(10):3482–3489. doi: 10.1128/mcb.7.10.3482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Quantin B., Breathnach R. Epidermal growth factor stimulates transcription of the c-jun proto-oncogene in rat fibroblasts. Nature. 1988 Aug 11;334(6182):538–539. doi: 10.1038/334538a0. [DOI] [PubMed] [Google Scholar]
  22. Ryder K., Nathans D. Induction of protooncogene c-jun by serum growth factors. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8464–8467. doi: 10.1073/pnas.85.22.8464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schröter H., Shaw P. E., Nordheim A. Purification of intercalator-released p67, a polypeptide that interacts specifically with the c-fos serum response element. Nucleic Acids Res. 1987 Dec 23;15(24):10145–10158. doi: 10.1093/nar/15.24.10145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Simon M. C., Fisch T. M., Benecke B. J., Nevins J. R., Heintz N. Definition of multiple, functionally distinct TATA elements, one of which is a target in the hsp70 promoter for E1A regulation. Cell. 1988 Mar 11;52(5):723–729. doi: 10.1016/0092-8674(88)90410-2. [DOI] [PubMed] [Google Scholar]
  25. Treisman R. Identification and purification of a polypeptide that binds to the c-fos serum response element. EMBO J. 1987 Sep;6(9):2711–2717. doi: 10.1002/j.1460-2075.1987.tb02564.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Treisman R. The SRE: a growth factor responsive transcriptional regulator. Semin Cancer Biol. 1990 Feb;1(1):47–58. [PubMed] [Google Scholar]
  28. Treisman R. Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5' element and c-fos 3' sequences. Cell. 1985 Oct;42(3):889–902. doi: 10.1016/0092-8674(85)90285-5. [DOI] [PubMed] [Google Scholar]
  29. Unlap T., Franklin C. C., Wagner F., Kraft A. S. Upstream regions of the c-jun promoter regulate phorbol ester-induced transcription in U937 leukemic cells. Nucleic Acids Res. 1992 Feb 25;20(4):897–902. doi: 10.1093/nar/20.4.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wu B. Y., Fodor E. J., Edwards R. H., Rutter W. J. Nerve growth factor induces the proto-oncogene c-jun in PC12 cells. J Biol Chem. 1989 May 25;264(15):9000–9003. [PubMed] [Google Scholar]
  31. de Groot R. P., Pals C., Kruijer W. Transcriptional control of c-jun by retinoic acid. Nucleic Acids Res. 1991 Apr 11;19(7):1585–1591. doi: 10.1093/nar/19.7.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. de Groot R. P., Schoorlemmer J., van Genesen S. T., Kruijer W. Differential expression of jun and fos genes during differentiation of mouse P19 embryonal carcinoma cells. Nucleic Acids Res. 1990 Jun 11;18(11):3195–3202. doi: 10.1093/nar/18.11.3195. [DOI] [PMC free article] [PubMed] [Google Scholar]

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