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RelB, a new partner of aryl hydrocarbon receptor-mediated transcription.

Abstract : The nuclear factor-kappaB (NF-kappaB) transcription factor family has a crucial role in rapid responses to stress and pathogens. We show that the NF-kappaB subunit RelB is functionally associated with the aryl hydrocarbon receptor (AhR) and mediates transcription of chemokines such as IL-8 via activation of AhR and protein kinase A. RelB physically interacts with AhR and binds to an unrecognized RelB/AhR responsive element of the IL-8 promoter linking two signaling pathways to activate gene transcription. We found a time-dependent recruitment of AhR to the RelB/AhR responsive element site of IL-8 mediated by the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) and via activation of protein kinase A. Furthermore, NF-kappaB-binding sites that are preferentially recognized by RelB/p52 are a target for RelB/AhR complexes without addition of any stimuli, implicating the endogenous function of the AhR. RelB/AhR complexes are also found to bind on xenobiotic responsive element, and RelB drastically increases the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced xenobiotic responsive element reporter activity. The interaction of RelB with AhR signaling, and AhR with NF-kappaB RelB signaling pathways represent a new mechanism of cross talk between the two transcription factors.
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Submitted on : Monday, March 31, 2008 - 3:51:47 PM
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Christoph F. A. Vogel, Eric Sciullo, Wen Li, Pat Wong, Gwendal Lazennec, et al.. RelB, a new partner of aryl hydrocarbon receptor-mediated transcription.. Molecular Endocrinology -Baltimore-, Endocrine Society, 2007, 21 (12), pp.2941-55. ⟨10.1210/me.2007-0211⟩. ⟨inserm-00268250⟩



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