1: J Biol Chem. 2005 Jul 1;280(26):24356-62. Epub 2005 Apr 27. 

Role of CREB1 and NF{kappa}B-p65 in the down-regulation of renin gene expression
by tumor necrosis factor {alpha}.

Todorov VT, Volkl S, Friedrich J, Kunz-Schughart LA, Hehlgans T, Vermeulen L,
Haegeman G, Schmitz ML, Kurtz A.

Institute of Physiology, Institute of Pathology, and Department of Immunology,
Regensburg University, D-93040 Regensburg, Germany.
vladimir.todorov@vkl.uniregensburg.de

Tumor necrosis factor-alpha (TNFalpha) is a potent inhibitor of renin gene
expression in renal juxtaglomerular cells. We have found that TNFalpha
suppresses renin transcription via transcription factor NFkappaB, which targets
a cAMP responsive element (CRE) in the renin promoter. Here we aimed to further
clarify the role of NFkappaB 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 TNFalpha in the juxtaglomerular cell line
As4.1. TNFalpha caused a moderate decrease in the binding of CREB1 to its
cognate CRE DNA binding site. On the other hand, NFkappaB-p65 transcriptional
activity was substantially reduced by TNFalpha, which targeted a
trans-activation domain at the very C terminus of the p65 molecule. Our results
suggest that TNFalpha inhibits renin gene expression by decreasing the
transactivating capacity of NFkappaB-p65 and partially by attenuating CREB1
binding to CRE.

PMID: 15857826 [PubMed - indexed for MEDLINE]


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