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TCDD induces c-jun expression via a novel Ah (dioxin) receptor-mediated p38–MAPK-dependent pathway

Oncogene volume 24, pages 4975–4983 (2005)Cite this article

Abstract

The aryl hydrocarbon receptor (AhR) has a fundamental role during postnatal liver development and is essential for mediating dioxin toxicity. However, the genetic programs mediating, both, the toxic and physiological effects downstream of the transcription factor AhR are in major parts unknown. We have identified the proto-oncogene c-jun as a novel target gene of AhR. Induction of c-jun depends on activation of p38–mitogen-activated protein kinase (MAPK) by an AhR-dependent mechanism. None of the kinases that are known to phosphorylate p38-MAPK is activated by AhR. Neither the dephosphorylation rate of p38–MAPK is reduced. Furthermore, increased p38–MAPK phosphorylation in response to dioxins does not require ongoing transcription. These findings establish activating ‘cross-talk’ with MAPK signaling as a novel principle of AhR action, which is apparently independent of the AhR's function as a DNA-binding transcriptional activator.

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References

  • Bender K, Göttlicher M, Whiteside S, Rahmsdorf HJ and Herrlich P . (1998). EMBO J., 17, 5170–5181.

  • Burbach KM, Poland A and Bradfield CA . (1992). Proc. Natl. Acad. Sci. USA, 89, 8185–8189.

  • Cavigelli M, Li WW, Lin A, Su B, Yoshioka K and Karin M . (1996). EMBO J., 15, 6269–6279.

  • Chang L and Karin M . (2001). Nature, 410, 37–40.

  • Couture L, Abbott B and Birnbaum L . (1990). Teratology, 42, 619–627.

  • De Bosscher K, Vanden Berghe W and Haegeman G . (2003). Endocr. Rev., 24, 488–522.

  • Dunlap JC . (1998). Curr. Opin. Genet. Dev., 8, 400–406.

  • Ema M, Sogawa K, Watanabe N, Chujoh Y, Matsushita N, Gotoh O, Funae Y and Fujii-Kuriyama Y . (1992). Biochem. Biophys. Res. Commun., 184, 246–253.

  • Enan E and Matsumura F . (1995). Biochem. Pharmacol., 49, 249–261.

  • Fernandez-Salguero P, Pineau T, Hilbert DM, McPhail T, Lee SS, Kimura S, Nebert DW, Rudikoff S, Ward JM and Gonzalez FJ . (1995). Science, 268, 722–726.

  • Fernandez-Salguero PM, Hilbert DM, Rudikoff S, Ward JM and Gonzalez FJ . (1996). Toxicol. Appl. Pharmacol., 140, 173–179.

  • Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch RJ, Luo Y and Han J . (2002). Science, 295, 1291–1294.

  • Herrlich P . (2001). Oncogene, 20, 2465–2475.

  • Hoffer A, Chang CY and Puga A . (1996). Toxicol. Appl. Pharmacol., 141, 238–247.

  • Hoffman EC, Reyes H, Chu FF, Sander F, Conley LH, Brooks BA and Hankinson O . (1991). Science, 252, 954–958.

  • Huff J, Lucier G and Tritscher A . (1994). Annu. Rev. Pharmacol. Toxicol., 34, 343–372.

  • Jochum W, Passegue E and Wagner EF . (2001). Oncogene, 20, 2401–2412.

  • Knebel A, Rahmsdorf HJ, Ullrich A and Herrlich P . (1996). EMBO J., 15, 5314–5325.

  • Kolluri SK, Weiss C, Koff A and Göttlicher M . (1999). Genes Dev., 13, 1742–1753.

  • Leppä S and Bohmann D . (1999). Oncogene, 18, 6158–6162.

  • Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schütz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P and Evans R . (1995). Cell, 83, 835–839.

  • Marinissen MJ, Chiariello M and Gutkind JS . (2001). Genes Dev., 15, 535–553.

  • Matikainen T, Perez GI, Jurisicova A, Pru JK, Schlezinger JJ, Ryu HY, Laine J, Sakai T, Korsmeyer SJ, Casper RF, Sherr DH and Tilly JL . (2001). Nat. Genet., 28, 355–360.

  • McLachlan JA . (2001). Endocr. Rev., 22, 319–341.

  • Migliaccio A, Di Domenico M, Castoria G, de Falco A, Bontempo P, Nola E and Auricchio F . (1996). EMBO J., 15, 1292–1300.

  • Migliaccio A, Piccolo D, Castoria G, Di Domenico M, Bilancio A, Lombardi M, Gong W, Beato M and Auricchio F . (1998). EMBO J., 17, 2008–2018.

  • Nebert DW . (1994). Biochem. Pharmacol., 47, 25–37.

  • Nebert DW, Puga A and Vasiliou V . (1993). Ann. NY. Acad. Sci., 685, 624–640.

  • Noselli S and Perrimon N . (2000). Science, 290, 68–69.

  • Ogawa S, Lozach J, Jepsen K, Sawka-Verhelle D, Perissi V, Sasik R, Rose DW, Johnson RS, Rosenfeld MG and Glass CK . (2004). Proc. Natl. Acad. Sci. USA, 101, 14461–14466.

  • Peterson RE, Theobald HM and Kimmel GL . (1993). Crit. Rev. Toxicol., 23, 283–335.

  • Puga A, Nebert DW and Carrier F . (1992). DNA Cell Biol., 11, 269–281.

  • Reyes H, Reisz-Porszasz S and Hankinson O . (1992). Science, 256, 1193–1195.

  • Schmidt JV and Bradfield CA . (1996). Ann. Rev. Cell. Dev. Biol., 12, 55–89.

  • Suskind RR . (1985). Scand. J. Work Environ. Health, 11, 165–171.

  • Swanson HI and Bradfield CA . (1993). Pharmacogenetics, 3, 213–230.

  • van Dam H and Castellazzi M . (2001). Oncogene, 20, 2453–2464.

  • Vanden Heuvel JP and Lucier G . (1993). Environ. Health Perspect., 100, 189–200.

  • Vogt PK . (2001). Oncogene, 20, 2365–2377.

  • Wada T and Penninger JM . (2004). Oncogene, 23, 2838–2849.

  • Weiss C and Bohmann D . (2004). Cell Cycle, 3, 111–113.

  • Weiss C, Kolluri SK, Kiefer F and Göttlicher M . (1996). Exp. Cell Res., 226, 154–163.

  • Weiss C, Schneider S, Wagner EF, Zhang X, Seto E and Bohmann D . (2003). EMBO J., 22, 3686–3695.

  • Werling U, Siehler S, Litfin M, Nau H and Göttlicher M . (2001). Mol. Pharmacol., 59, 1269–1276.

  • Zugerman C . (1990). Dermatol. Clin., 8, 209–213.

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Acknowledgements

We thank Dirk Bohmann and Catherine Ovitt for critical reading of the manuscript and Elke Martin for technical assistance.

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Authors and Affiliations

  1. Institute of Toxicology, University of Mainz, Mainz, 55131, Germany

    Carsten Weiss, Dagmar Faust, Heike Dürk, Cornelia Dietrich & Franz Oesch

  2. Institute of Toxicology and Genetics, Forschungszentrum Karlsruhe, Karlsruhe, 76021, Germany

    Carsten Weiss, Siva Kumar Kolluri, Anke Pelzer, Sandra Schneider & Martin Göttlicher

  3. The Burnham Institute, Cancer Center, La Jolla, 92037, CA

    Siva Kumar Kolluri

  4. Department of Food Chemistry and Toxicology, University of Karlsruhe, Karlsruhe, 76128, Germany

    Anke Pelzer

  5. Institute of Toxicology, GSF National Research Center for Environment and Health, Neuherberg, 85764, Germany

    Martin Göttlicher

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  1. Carsten Weiss
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Correspondence to Carsten Weiss or Martin Göttlicher.

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Weiss, C., Faust, D., Dürk, H. et al. TCDD induces c-jun expression via a novel Ah (dioxin) receptor-mediated p38–MAPK-dependent pathway. Oncogene 24, 4975–4983 (2005). https://doi.org/10.1038/sj.onc.1208679

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