Role of CREB1 and NFκB-p65 in the Down-regulation of Renin Gene Expression by Tumor Necrosis Factor Î
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 clarif...
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Veröffentlicht in: | The Journal of biological chemistry 2005-07, Vol.280 (26), p.24356 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M502968200 |