Nrf1 in a complex with fosB, c-jun, junD and ATF2 forms the AP1 component at the TNF  promoter in stimulated mast cells

Abstract

Cap 'n' collar-basic leucine zipper (CNC-bZIP) proteins are widely implicated in developmental processes throughout different species. Evidence is accumulating that some of them are also participating in induced gene expression in the adult. Here we show that the three CNC-bZIP members NF-E2, Nrf1 and Nrf2 are constitutively expressed in the murine mast cell line CPII and that they form transcription factor complexes with several AP1 binding proteins. Upon induction, complexes are observed at the 2 x NF-E2 consensus binding site and the extended kappa3/AP1(+) site of the TNFalpha promoter. The interaction of Nrf1 with c -jun, junD, fosB and ATF2 in mast cells is in contrast to the recently reported binding of Nrf1 alone at the kappa3/AP1(-) site in dendritic cells. We speculated that this may be the result of the expression of isoforms of Nrf1 in mast cells. Using a PCR cloning strategy, we have isolated six novel splice variants of this transcription factor. Some of them have deleted the translational stop codon, resulting in an Nrf1 protein with an altered leucine zipper region. Expression of this altered binding/interaction domain interferes with TNFalpha induction, indicating an interaction of this splice variant with the active AP1/NF-AT complex at this promoter.

Mitogen activated protein kinases: a role in inflammatory bowel disease?

“…This transcription factor, along with c-Fos, FosB, FOSL1/2, JunB, JunD and c-MAF, are members of the AP-1 family of transcription factors [54]. Once activated by phosphorylation they can form hetero-or homodimers, and can induce the transcription of many genes including cytokines, which has been shown for several different tissues, for example lung epithelial cells and mast cells, to produce TNF-a and ILs, which are potent mediators of various inflammatory conditions including IBD [55][56][57].…”

Is there a future for TNF promoter polymorphisms?

“…18 No SNPs have been identified in this proximal portion of the promoter, where they might be expected to be able to influence transcription, while those that have been reported, all occur in regions that have no clearly established functional significance. Most of the factors that have been convincingly described as being involved in TNF transcription, including CREB, 157 C/EBPa þ b, [158][159][160] NFATp, [161][162][163] SP-1, Egr-1, 164 ATF2/JUN, 162,163,165,166 Nrf-1, 167,168 and Ets, 169 bind within the 200 bp proximal promoter. Although functional binding sites in the À600 region have been reported for NF-kB 170,171 and Litaf, 172,173 these regions harbour no known SNP.…”

TCF11 at the crossroads of oxidative stress and the ubiquitin proteasome system

“…1). 42,66,67 intra-membrane cleavage, releasing the transcriptional active cytoplasmic part. However, Zhang and colleagues found no evidence for S1P and S2P cleavage of TCF11.…”