Structure and dynamics of the kinase IKK-β – A key regulator of the NF-kappa B transcription factor

Previous studies demonstrated that respiratory syncytial virus (RSV) infection of A549 cells induced interleukin (IL)-8 gene expression and protein release from the cells as early as 2 h after treatment [M. A. Fiedler, K. Wernke-Dollries, and J. M. Stark. Am. J. Physiol. 269 (Lung Cell. Mol. Physiol. 13): L865-L872, 1995; J. G. Mastronarde, M. M. Monick, and G. W. Hunninghake. Am. J. Respir. Cell Mol. Biol. 13: 237-244, 1995]. Furthermore, the effects of RSV at the 2-h time point were not dependent on viral replication. The studies reported here were designed to test the hypothesis that active and inactive RSV induce IL-8 gene expression in A549 cells at the 2-h time point by a mechanism dependent on the activation of the nuclear transcription factor NF-kappa B Northern blot analysis indicated that IL-8 gene expression occurred independent of protein synthesis 2 h after A549 cells were treated with RSV. Analysis of nuclear extracts from RSV-treated A549 cells by electrophoretic mobility shift assays demonstrated that NF-kappa B was activated as early as 15 min after RSV was added to the cells and remained activated for at least 90 min. In contrast, baseline levels of NF-IL-6 and activator protein-1 (AP-1) did not change over this period of time. Deoxyribonuclease footprint analysis of a portion of the 5'-flanking region of the IL-8 gene demonstrated two potential regions for transcription factor binding, which corresponded to the potential AP-1 binding site, and potential NF-IL-6 and NF-kappa B binding sites. Mutational analysis of the 200-bp 5'-untranslated region of the IL-8 gene demonstrated that activation of NF-kappa B and NF-IL-6 were required for RSV-induced transcriptional activation of the IL-8 gene.

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Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1.

The EMBO Journal ◽

10.1002/j.1460-2075.1991.tb07761.x ◽

1991 ◽

Vol 10 (8) ◽

pp. 2247-2258 ◽

Cited By ~ 2663

Author(s):

R. Schreck ◽

P. Rieber ◽

P.A. Baeuerle

Keyword(s):

Transcription Factor ◽

Reactive Oxygen ◽

Reactive Oxygen Intermediates ◽

Nf Kappa B ◽

Oxygen Intermediates ◽

Hiv 1

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NF-kappa B as inducible transcriptional activator of the granulocyte-macrophage colony-stimulating factor gene.

Molecular and Cellular Biology ◽

10.1128/mcb.10.3.1281 ◽

1990 ◽

Vol 10 (3) ◽

pp. 1281-1286 ◽

Cited By ~ 131

Author(s):

R Schreck ◽

P A Baeuerle

Keyword(s):

T Cells ◽

Transcription Factor ◽

T Cell ◽

Interleukin 2 ◽

Colony Stimulating Factor ◽

Nf Kappa B ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

The expression of the gene encoding the granulocyte-macrophage colony-stimulating factor (GM-CSF) is induced upon activation of T cells with phytohemagglutinin and active phorbolester and upon expression of tax1, a transactivating protein of the human T-cell leukemia virus type I. The same agents induce transcription from the interleukin-2 receptor alpha-chain and interleukin-2 genes, depending on promoter elements that bind the inducible transcription factor NF-kappa B (or an NF-kappa B-like factor). We therefore tested the possibility that the GM-CSF gene is also regulated by a cognate motif for the NF-kappa B transcription factor. A recent functional analysis by Miyatake et al. (S. Miyatake, M. Seiki, M. Yoshida, and K. Arai, Mol. Cell. Biol. 8:5581-5587, 1988) described a short promoter region in the GM-CSF gene that conferred strong inducibility by T-cell-activating signals and tax1, but no NF-kappa B-binding motifs were identified. Using electrophoretic mobility shift assays, we showed binding of purified human NF-kappa B and of the NF-kappa B activated in Jurkat T cells to an oligonucleotide comprising the GM-CSF promoter element responsible for mediating responsiveness to T-cell-activating signals and tax1. As shown by a methylation interference analysis and oligonucleotide competition experiments, purified NF-kappa B binds at positions -82 to -91 (GGGAACTACC) of the GM-CSF promoter sequence with an affinity similar to that with which it binds to the biologically functional kappa B motif in the beta interferon promoter (GGGAAATTCC). Two kappa B-like motifs at positions -98 to -108 of the GM-CSF promoter were also recognized but with much lower affinities. Our data provide strong evidence that the expression of the GM-CSF gene following T-cell activation is controlled by binding of the NF-kappa B transcription factor to a high-affinity binding site in the GM-CSF promoter.

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Involvement of a NF-kappa B-like transcription factor in the activation of the interleukin-6 gene by inflammatory lymphokines

Molecular and Cellular Biology ◽

10.1128/mcb.10.2.561-568.1990 ◽

1990 ◽

Vol 10 (2) ◽

pp. 561-568

Author(s):

H Shimizu ◽

K Mitomo ◽

T Watanabe ◽

S Okamoto ◽

K Yamamoto

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcriptional Activation ◽

Interleukin 6 ◽

Interleukin 1 ◽

Tnf Alpha ◽

Nuclear Factor ◽

Nf Kappa B ◽

Necrosis Factor Alpha ◽

Mediators Of Inflammation

Interleukin-6 (IL-6) is one of the major mediators of inflammation, and its expression is inducible by the other inflammatory lymphokines, interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). We demonstrate that a common IL-6 promoter element, termed inflammatory lymphokine-responsive element (ILRE), is important for induction of IL-6 gene expression by IL-1 and TNF-alpha despite possible differences in the mechanisms of action of these lymphokines. Remarkably, the ILRE sequence, located between -73 to -63 relative to the mRNA cap site, is highly homologous to NF-kappa B transcription factor-binding motifs and binds an IL-1-TNF-alpha-inducible nuclear factor; the sequence specificities, binding characteristics, and subcellular localizations of this factor are indistinguishable from those of NF-kappa B. In addition, mutations of the ILRE sequence which impair the binding of this nuclear factor abolished the induction of IL-6 gene expression by IL-1 and TNF-alpha in vivo. These results indicate that a nuclear factor indistinguishable from NF-kappa B is involved in the transcriptional activation of the IL-6 gene by IL-1 and TNF-alpha.

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Transcription factor NF-kappa B represses ANT1 transcription and leads to mitochondrial dysfunctions

Scientific Reports ◽

10.1038/srep44708 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 11

Author(s):

Chen Zhang ◽

Hui Jiang ◽

Pin Wang ◽

Heng Liu ◽

Xiulian Sun

Keyword(s):

Transcription Factor ◽

Nf Kappa B ◽

Mitochondrial Dysfunctions

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Cyclic AMP-independent activation of transcription factor NF-kappa B in HL60 cells by tumor necrosis factors alpha and beta.

Molecular and Cellular Biology ◽

10.1128/mcb.11.4.2315 ◽

1991 ◽

Vol 11 (4) ◽

pp. 2315-2318 ◽

Cited By ~ 16

Author(s):

H P Hohmann ◽

R Kolbeck ◽

R Remy ◽

A P van Loon

Keyword(s):

Transcription Factor ◽

Tumor Necrosis Factor ◽

Cyclic Amp ◽

Tumor Necrosis ◽

Tnf Alpha ◽

Nf Kappa B ◽

Tumor Necrosis Factors ◽

Hl60 Cells ◽

Activation Of Transcription ◽

Necrosis Factor

No correlation exists in HL60 cells between NF-kappa B activation by tumor necrosis factor (TNF alpha) and TNF beta and intracellular levels of cyclic AMP. Cyclic AMP levels did not increase upon treatment of cells with each of these cytokines, although NF-kappa B was activated. Forskolin or 1-isobutyl-3-methylxanthine drastically increased intracellular levels of cyclic AMP, but neither activated NF-kappa B nor influenced TNF-induced NF-kappa B activation.

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