Role of CREB1 and NFκB-p65 in the Down-regulation of Renin Gene Expression by Tumor Necrosis Factor α

Tumor necrosis factor-α (TNFα) is a potent inhibitor of renin gene expression in renal juxtaglomerular cells. We have found that TNFα suppresses renin transcription via transcription factor NFκB, which targets a cAMP responsive element (CRE) in the renin promoter. Here we aimed to further clarify th...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-07, Vol.280 (26), p.24356-24362
Main Authors: Todorov, Vladimir T., Völkl, Simon, Friedrich, Jürgen, Kunz-Schughart, Leoni A., Hehlgans, Thomas, Vermeulen, Linda, Haegeman, Guy, Schmitz, M. Lienhard, Kurtz, Armin
Format: Article
Language:English
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Summary:Tumor necrosis factor-α (TNFα) is a potent inhibitor of renin gene expression in renal juxtaglomerular cells. We have found that TNFα suppresses renin transcription via transcription factor NFκB, which targets a cAMP responsive element (CRE) in the renin promoter. Here we aimed to further clarify the role of NFκB and the canonical CRE-binding proteins of the CRE-binding protein/activating transcription factor (CREB/ATF) family in the inhibition of renin gene expression by TNFα in the juxtaglomerular cell line As4.1. TNFα caused a moderate decrease in the binding of CREB1 to its cognate CRE DNA binding site. On the other hand, NFκB-p65 transcriptional activity was substantially reduced by TNFα, which targeted a trans-activation domain at the very C terminus of the p65 molecule. Our results suggest that TNFα inhibits renin gene expression by decreasing the transactivating capacity of NFκB-p65 and partially by attenuating CREB1 binding to CRE.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M502968200