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TCDD induces c-jun expression via a novel Ah (dioxin) receptor-mediated p38 MAPK-dependent pathway
被引:78
作者:
Weiss, C
Faust, D
Dürk, H
Kolluri, SK
Pelzer, A
Schneider, S
Dietrich, C
Oesch, F
Göttlicher, M
机构:
[1] Johannes Gutenberg Univ Mainz, Inst Toxicol, D-55131 Mainz, Germany
[2] Forschungszentrum Karlsruhe, Inst Toxicol & Genet, D-76021 Karlsruhe, Germany
[3] Burnham Inst, Ctr Canc, La Jolla, CA 92037 USA
[4] Univ Karlsruhe, Dept Food Chem & Toxicol, D-76128 Karlsruhe, Germany
[5] GSF, Natl Res Ctr Environm & Hlth, Inst Toxicol, D-85764 Neuherberg, Germany
来源:
关键词:
p38 MAP kinase;
c-jun;
Ah receptor;
dioxin;
cross-talk;
TCDD;
D O I:
10.1038/sj.onc.1208679
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
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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页码:4975 / 4983
页数:9
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