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The constitutive activation of the CEF-4/9E3 chemokine gene depends on C/EBPβ in v-src transformed chicken embryo fibroblasts

Oncogene volume 20, pages 2301–2313 (2001)Cite this article

Abstract

The CEF-4/9E3 chemokine gene is expressed constitutively in chicken embryo fibroblasts (CEF) transformed by the Rous sarcoma virus (RSV). This aberrant induction is controlled at the transcriptional and post-transcriptional levels. Transcriptional activation depends on multiple elements of the CEF-4 promoter composing a Src-responsive-Unit or SRU. The SRU includes a TPA responsive element, a PRDII/κB domain and a CAAT box. In this report, we identify C/EBPβ as a component of the trans-acting factor interacting with the CAAT box of the CEF-4 promoter. In addition, we show that C/EBPβ binds to a second element located in proximity of the TRE. A mutation of this distal CAAT box impaired the activation of the CEF-4 promoter by pp60v-src indicating that this element is also part of the SRU. Using the RCASBP retroviral vector, we expressed a dominant negative mutant of C/EBPβ (designated Δ184-C/EBPβ) in RSV-transformed CEF. Δ184-C/EBPβ decreased the accumulation of the CEF-4 mRNA and activation of the CEF-4 promoter by pp60v-src. The induction of the Cox-2 gene (CEF-147) was also reduced by Δ184-C/EBPβ. The effect of the dominant negative mutant was observed within 1 h of the activation of a thermolabile pp60v-src suggesting that C/EBPβ is an early target of v-src transformation. The dominant negative mutant did not inhibit the transformation of CEF by RSV and in fact accentuated the transformed cell phenotype. Therefore, the activation of C/EBPβ is important for the expression of v-src regulated genes but is not required for the in vitro transformation of CEF by pp60v-src.

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References

  • Arenberg DA, Kunkel SL, Polverini PJ, Glass M, Burdick MD, Strieter RM . 1996 J. Clin. Invest. 97: 2792–2802

  • Balentien E, Mufson BE, Shattuck RL, Derynck R, Richmond A . 1991 Oncogene 6: 1115–1124

  • Bedard PA, Alcorta D, Simmons DL, Luk KC, Erikson RL . 1987a Proc. Natl. Acad. Sci. USA 84: 6715–6719

  • Bedard PA, Balk SD, Gunther HS, Morisi A, Erikson RL . 1987b Mol. Cell Biol. 7: 1450–1458

  • Briggs MR, Kadonaga JT, Bell SP, Tjian R . 1986 Science 234: 47–52

  • Bromberg JF, Horvath CM, Besser D, Lathem WW, Darnell Jr. JE . 1998 Mol. Cell Biol. 18: 2553–2558

  • Bruder JT, Heidecker G, Rapp UR . 1992 Genes Dev. 6: 545–556

  • Buck M, Poli V, van der Geer P, Chojkier M, Hunter T . 1999 Mol. Cell. 4: 1087–1092

  • Cabannes E, Vives MF, Bedard PA . 1997 Oncogene 15: 29–43

  • Calkhoven CF, Bouwman PR, Snippe L, Ab G . 1994 Nucleic Acids Res. 22: 5540–5547

  • Calkhoven CF, Muller C, Leutz A . 2000 Genes Dev. 14: 1920–1932

  • Chang CJ, Chen YL, Lee SC . 1998 Mol. Cell Biol. 18: 5880–5887

  • Dehbi M, Bedard PA . 1992 Biochem. Cell Biol. 70: 980–997

  • Dehbi M, Mbiguino A, Beauchemin M, Chatelain G, Bedard PA . 1992 Mol. Cell Biol. 12: 1490–1499

  • Dignam JD, Lebovitz RM, Roeder RG . 1983 Nucleic Acids Res. 11: 1475–1489

  • Gillet G, Guerin M, Trembleau A, Brun G . 1995 EMBO J. 14: 1372–1381

  • Granger-Schnarr M, Benusiglio E, Schnarr M, Sassone-Corsi P . 1992 Proc. Natl. Acad. Sci. USA 89: 4236–4239

  • Greenbaum LE, Li W, Cressman DE, Peng Y, Ciliberto G, Poli V, Taub R . 1998 J. Clin. Invest. 102: 996–1007

  • Haghnegahdar H, Du J, Wang D, Strieter RM, Burdick MD, Nanney LB, Cardwell N, Luan J, Shattuck-Brandt R, Richmond A . 2000 J. Leukoc. Biol. 67: 53–62

  • Hsu W, Kerppola TK, Chen PL, Curran T, Chen-Kiang S . 1994 Mol. Cell Biol. 14: 268–276

  • Inoue H, Pan J, Hakura A . 1998 J. Virol. 72: 2532–2537

  • Johnson R, Spiegelman B, Hanahan D, Wisdom R . 1996 Mol. Cell Biol. 16: 4504–4511

  • Joseph CK, Qureshi SA, Wallace DJ, Foster DA . 1992 J. Biol. Chem. 267: 1327–1330

  • Katz S, Kowenz-Leutz E, Muller C, Meese K, Ness SA, Leutz A . 1993 EMBO J. 12: 1321–1332

  • Kim Y, Fisher SM . 1998 J. Biol. Chem. 273: 27686–27694

  • Kim S, Mao PL, Gagliardi M, Bedard PA . 1999 Mol. Cell Biol. 19: 5718–5731

  • Klampfer L, Lee TH, Hsu W, Vilcek J, Chen-Kiang S . 1994 Mol. Cell Biol. 14: 6561–6569

  • Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA, Elner VM, Elner SG, Strieter RM . 1992 Science 258: 1798–1801

  • Kowenz-Leutz E, Leutz A . 1999 Mol. Cell 4: 735–743

  • Kowenz-Leutz E, Twamley G, Ansieau S, Leutz A . 1994 Genes Dev. 8: 2781–2791

  • LeClair KP, Blanar MA, Sharp PA . 1992 Proc. Natl. Acad. Sci. USA 89: 8145–8149

  • Lin X, Gelman IH . 1997 [published errata appear in Cancer Res., 1997 Jul 15;57(14):3068 and 1998 Apr 15;58(8):1770] Cancer Res. 57: 2304–2312

  • Lin X, Tombler E, Nelson PJ, Ross M, Gelman IH . 1996 J. Biol. Chem. 271: 28430–28438

  • Lloyd A, Yancheva N, Wasylyk B . 1991 Nature 352: 635–638

  • Mangeney M, Schmitt JR, Leverrier Y, Thomas J, Marvel J, Brun G, Gillet G . 1996 Oncogene 13: 1441–1446

  • Mao PL, Beauchemin M, Bedard PA . 1993 J. Biol. Chem. 268: 8131–8139

  • Martins-Green M, Feugate JE . 1998 Cytokine 10: 522–535

  • Martins-Green M, Hanafusa H . 1997 Cytokine Growth Factor Rev. 8: 221–232

  • Matsusaka T, Fujikawa K, Nishio Y, Mukaida N, Matsushima K, Kishimoto T, Akira S . 1993 Proc. Natl. Acad. Sci. USA 90: 10193–10197

  • Merika M, Williams AJ, Chen G, Collins T, Thanos D . 1998 Mol. Cell 1: 277–287

  • Mink S, Haenig B, Klempnauer KH . 1997 Mol. Cell Biol. 17: 6609–6617

  • Muller C, Alunni-Fabbroni M, Kowenz-Leutz E, Mo X, Tommasino M, Leutz A . 1999 Proc. Natl. Acad. Sci. USA 96: 7276–7281

  • Petropoulos CJ, Hughes SH . 1991 J. Virol. 65: 3728–3737

  • Raught B, Gingras AC, James A, Medina D, Sonenberg N, Rosen JM . 1996 Cancer Res. 56: 4382–4386

  • Richmond A, Balentien E, Thomas HG, Flaggs G, Barton DE, Spiess J, Bordoni R, Francke U, Derynck R . 1988 EMBO J. 7: 2025–2033

  • Robinson GW, Johnson PF, Hennighausen L, Sterneck E . 1998 Genes Dev. 12: 1907–1916

  • Schadendorf D, Moller A, Algermissen B, Worm M, Sticherling M, Czarnetzki BM . 1993 [published erratum appears in J. Immunol., 1994 Oct 1;153(7):3360] J. Immunol. 151: 2667–2675

  • Seagroves TN, Lydon JP, Hovey RC, Vonderhaar BK, Rosen JM . 2000 Mol. Endocrinol 14: 359–368

  • Sears RC, Sealy L . 1992 J. Virol. 66: 6338–6352

  • Sears RC, Sealy L . 1994 [published erratum appears in Mol. Cell Biol., 1994 Aug;14(8):5617] Mol. Cell Biol. 14: 4855–4871

  • Simmons DL, Levy DB, Yannoni Y, Erikson RL . 1989 Proc. Natl. Acad. Sci. USA 86: 1178–1182

  • Stein B, Cogswell PC, Baldwin Jr. AS . 1993 Mol. Cell Biol. 13: 3964–3974

  • Sterneck E, Muller C, Katz S, Leutz A . 1992 EMBO J. 11: 115–126

  • Sugano S, Stoeckle MY, Hanafusa H . 1987 Cell 49: 321–328

  • Sunderkotter C, Steinbrink K, Goebeler M, Bhardwaj R, Sorg C . 1994 J. Leukoc. Biol. 55: 410–422

  • Suzuki T, Murakami M, Onai N, Fukuda E, Hashimoto Y, Sonobe MH, Kameda T, Ichinose M, Miki K, Iba H . 1994 J. Virol. 68: 3527–3535

  • Timchenko NA, Welm AL, Lu X, Timchenko LT . 1999 Nucleic Acids Res. 27: 4517–4525

  • Timchenko NA, Wilde M, Nakanishi M, Smith JR, Darlington GJ . 1996 Genes. Dev. 10: 804–815

  • Topol LZ, Marx M, Laugier D, Bogdanova NN, Boubnov NV, Clausen PA, Calothy G, Blair DG . 1997 Mol. Cell Biol. 17: 4801–4810

  • Turkson J, Bowman T, Garcia R, Caldenhoven E, De Groot RP, Jove R . 1998 Mol. Cell Biol. 18: 2545–2552

  • Wadleigh DJ, Reddy ST, Kopp E, Ghosh S, Herschman HR . 2000 J. Biol. Chem. 275: 6259–6266

  • Wakabayashi Y, Shono T, Isono M, Hori S, Matsushima K, Ono M, Kuwano M . 1995 Jpn. J. Cancer Res. 86: 1189–1197

  • Wasylyk C, Maira SM, Sobieszczuk P, Wasylyk B . 1994 Oncogene 9: 3665–3673

  • Xie WL, Chipman JG, Robertson DL, Erikson RL, Simmons DL . 1991 Proc. Natl. Acad. Sci. USA 88: 2692–2696

  • Xie W, Fletcher BS, Anderson RD, Herschman HR . 1994 Mol. Cell Biol. 14: 6531–6539

  • Yoshida S, Ono M, Shono T, Izumi H, Ishibashi T, Suzuki H, Kuwano M . 1997 Mol. Cell Biol. 17: 4015–4023

  • Zagariya A, Mungre S, Lovis R, Birrer M, Ness S, Thimmapaya B, Pope R . 1998 Mol. Cell Biol. 18: 2815–2824

  • Zhu S, Oh HS, Shim M, Sterneck E, Johnson PF, Smart RC . 1999 Mol. Cell Biol. 19: 7181–7190

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Acknowledgements

We thank Dr C Calkhoven for the avian C/EBPα clone, Dr A Leutz for providing expression constructs for avian C/EBPβ, Dr S Hughes for the RCASBP retroviral vectors, Dr Germain Gillet for providing clone NR-13 and Dr Dan Simmons for the Cox-2 cDNA. We are indebted to Dr E Cabannes for preparation of the RCASBP-C/EBPβ construct and G Temple for preparation of the figures. This work was funded by a grant from the Canadian Institute for Health Research to P-A Bédard.

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  1. Mark Gagliardi and Scott Maynard: M Gagliardi and S Maynard contributed equally to this work

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  1. Department of Biology, York University, 4700 Keele Street, Toronto, M3J 1P3, Ontario, Canada

    Mark Gagliardi, Scott Maynard & Pierre-André Bédard

  2. Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, L8S 4K1, Ontario, Canada

    Bojana Bojovic

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Gagliardi, M., Maynard, S., Bojovic, B. et al. The constitutive activation of the CEF-4/9E3 chemokine gene depends on C/EBPβ in v-src transformed chicken embryo fibroblasts. Oncogene 20, 2301–2313 (2001). https://doi.org/10.1038/sj.onc.1204354

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