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

1991 ◽  
Vol 11 (4) ◽  
pp. 2315-2318 ◽  
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.

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

1991 ◽  
Vol 11 (4) ◽  
pp. 2315-2318
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.

scholarly journals A novel tumor necrosis factor-responsive transcription factor which recognizes a regulatory element in hemopoietic growth factor genes.

1990 ◽  
Vol 10 (6) ◽  
pp. 2950-2959 ◽  
Author(s):  
M F Shannon ◽  
L M Pell ◽  
M J Lenardo ◽  
E S Kuczek ◽  
F S Occhiodoro ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Common Element ◽  
Tnf Alpha ◽  
Nf Kappa B ◽  
Gm Csf ◽  
Hemopoietic Growth Factor ◽  
Necrosis Factor

A conserved DNA sequence element, termed cytokine 1 (CK-1), is found in the promoter regions of many hemopoietic growth factor (HGF) genes. Mutational analyses and modification interference experiments show that this sequence specifically binds a nuclear transcription factor, NF-GMa, which is a protein with a molecular mass of 43 kilodaltons. It interacts with different affinities with the CK-1-like sequence from a number of HGF genes, including granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte (G)-CSF, interleukin 3 (IL-3), and IL-5. We show here that the level of NF-GMa binding is induced in embryonic fibroblasts by tumor necrosis factor-alpha (TNF-alpha) treatment and that the CK-1 sequence from the G-CSF gene is a TNF-alpha-responsive enhancer in these cells. The NF-GMa protein is distinct from another TNF-alpha-responsive transcription factor, NF-kappa B, by several criteria. Firstly, several NF-kappa B-binding sites, although having sequence similarity with the CK-1 sequence, cannot compete efficiently for NF-GMa binding to CK-1. Secondly, the CK-1 sequence from both G-CSF and GM-CSF does not respond to phorbol ester treatment as would an NF-kappa B-binding element. These results demonstrate that NF-GMa is a novel transcription factor inducible by TNF-alpha and binds to a common element in HGF gene promoters.

A novel tumor necrosis factor-responsive transcription factor which recognizes a regulatory element in hemopoietic growth factor genes

1990 ◽  
Vol 10 (6) ◽  
pp. 2950-2959
Author(s):  
M F Shannon ◽  
L M Pell ◽  
M J Lenardo ◽  
E S Kuczek ◽  
F S Occhiodoro ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Common Element ◽  
Tnf Alpha ◽  
Nf Kappa B ◽  
Gm Csf ◽  
Hemopoietic Growth Factor ◽  
Necrosis Factor

A conserved DNA sequence element, termed cytokine 1 (CK-1), is found in the promoter regions of many hemopoietic growth factor (HGF) genes. Mutational analyses and modification interference experiments show that this sequence specifically binds a nuclear transcription factor, NF-GMa, which is a protein with a molecular mass of 43 kilodaltons. It interacts with different affinities with the CK-1-like sequence from a number of HGF genes, including granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte (G)-CSF, interleukin 3 (IL-3), and IL-5. We show here that the level of NF-GMa binding is induced in embryonic fibroblasts by tumor necrosis factor-alpha (TNF-alpha) treatment and that the CK-1 sequence from the G-CSF gene is a TNF-alpha-responsive enhancer in these cells. The NF-GMa protein is distinct from another TNF-alpha-responsive transcription factor, NF-kappa B, by several criteria. Firstly, several NF-kappa B-binding sites, although having sequence similarity with the CK-1 sequence, cannot compete efficiently for NF-GMa binding to CK-1. Secondly, the CK-1 sequence from both G-CSF and GM-CSF does not respond to phorbol ester treatment as would an NF-kappa B-binding element. These results demonstrate that NF-GMa is a novel transcription factor inducible by TNF-alpha and binds to a common element in HGF gene promoters.

scholarly journals Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B.

1990 ◽  
Vol 10 (4) ◽  
pp. 1498-1506 ◽  
Author(s):  
M A Collart ◽  
P Baeuerle ◽  
P Vassalli
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Nf Kappa B ◽  
Necrosis Factor Alpha ◽  
Protein Subunits ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Stimulation Of

This study characterizes the interaction of murine macrophage nuclear proteins with the tumor necrosis factor alpha (TNF-alpha) promoter. Gel retardation and methylation interference assays showed that stimulation of TNF-alpha gene transcription in peritoneal exudate macrophages was accompanied by induction of DNA-binding proteins that recognized with different affinities four elements related to the kappa B consensus motif and a Y-box motif. We suggest that the basal level of TNF-alpha expression in macrophages is due to the binding of a constitutive form of NF-kappa B, present at low levels in nuclei from resting thioglycolate exudate peritoneal macrophages, to some if not all of the kappa B motifs; we postulate that this constitutive form contains only the 50-kilodalton (kDa) DNA-binding protein subunits of NF-kappa B, not the 65-kDa protein subunits (P. Baeuerle and D. Baltimore, Genes Dev. 3:1689-1698, 1989). Agents such as glucocorticoids, which decrease TNF-alpha transcription, diminished the basal level of nuclear NF-kappa B. Stimulation of Stimulation of TNF-alpha transcription in macrophages by lipopolysaccharide, gamma interferon, or cycloheximide led to an increased content of nuclear NF-kappa B. This induced factor represents a different form of NF-kappa B, since it generated protein-DNA complexes of slower mobility; we propose that this induced form of NF-kappa B contains both the 50- and 65-kDa protein subunits, the latter ones being necessary to bind NF-kappa B to its cytoplasmic inhibitor in uninduced cells (Baeuerle and Baltimore, Genes Dev., 1989). In resting cells, this inducible form of NF-kappa B was indeed detectable in the cytosol after deoxycholate treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Requirement for nuclear factor (NF)-kappa B p65 and NF-interleukin-6 binding elements in the tumor necrosis factor response region of the granulocyte colony-stimulating factor promoter

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2469-2479 ◽  
Author(s):  
SM Dunn ◽  
LS Coles ◽  
RK Lang ◽  
S Gerondakis ◽  
MA Vadas ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Nuclear Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Nf Kappa B ◽  
Stimulating Factor ◽  
Necrosis Factor ◽  
Response Region

Abstract Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor produced by mesenchymal and myeloid cells following activation by inflammatory stimuli. It has previously been shown that a region of the G-CSF promoter, (-200 to -165) containing the decanucleotide CK-1 element and two repeated sequences that resemble nuclear factor (NF)- interleukin-6 (IL-6) binding sites, is required for activation of the G- CSF gene by tumor necrosis factor-alpha (TNF-alpha) and IL-1 beta. We now show that the NF-kappa B p65 protein can bind to and activate this TNF response region. There are several unusual features of this p65 interaction with the TNF response region. First, NF-kappa B p65 but not the related NF-kappa B p50 binds to the CK-1 element and a p50/65 hybrid protein that relies on the p50 rel homology domain for DNA binding does not transactivate the TNF response region. Second, p65 transactivation of this region is cell specific and requires not only its own binding site but also the NF-IL6 consensus sites. NF-IL6 also binds to the TNF response region of the G-CSF promoter. Electrophoretic mobility shift studies show that p65 and NF-IL6 can bind cooperatively to the TNF response region. The ability of this region to respond to TNF-alpha or p65 is correlated with the ability to form the p65/NF-IL6 ternary complex.

scholarly journals Tumor Necrosis Factor-α-induced Cell Killing and Activation of Transcription Factor NF-κB Are Uncoupled in L929 Cells

1998 ◽  
Vol 273 (29) ◽  
pp. 18117-18121 ◽  
Author(s):  
Steffen P. Hehner ◽  
Thomas G. Hofmann ◽  
Frank Ratter ◽  
Andreas Dumont ◽  
Wulf Dröge ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Cell Killing ◽  
L929 Cells ◽  
Activation Of Transcription ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Three NF-kappa B binding sites in the human E-selectin gene required for maximal tumor necrosis factor alpha-induced expression.

1994 ◽  
Vol 14 (9) ◽  
pp. 5820-5831 ◽  
Author(s):  
U Schindler ◽  
V R Baichwal
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Binding Sites ◽  
Tumor Necrosis ◽  
Regulatory Elements ◽  
Tnf Alpha ◽  
Nf Kappa B ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Transcription of the gene encoding the endothelial cell-leukocyte adhesion molecule (ELAM-1; E-selectin) is induced in response to various cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1. A DNase I-hypersensitive site in the 5' proximal promoter region of the E-selectin gene is observed in human umbilical vein endothelial cells only following TNF-alpha treatment, suggesting the presence of a TNF-alpha-inducible element close to the transcriptional start site. Transient transfection studies in endothelial cells demonstrated that 170 bp of upstream sequences is sufficient to confer TNF-alpha inducibility. Systematic site-directed mutagenesis of this region revealed two regulatory elements (-129 to -110 and -99 to -80) that are essential for maximal promoter activity following cytokine treatment. Protein binding studies with crude nuclear extracts and recombinant proteins revealed that the two elements correspond to three NF-kappa B binding sites (site 1, -126; site 2, 116; and site 3, -94). All three sites can be bound by NF-kappa B when used as independent oligonucleotides in mobility shift assays. However, within the context of a larger promoter fragment, sites 2 and 3 are preferentially occupied over site 1. These data are consistent with results obtained in transfection studies demonstrating that mutations in sites 2 and 3 are more detrimental than mutations within site 1. Hence, inducibility of the E-selectin gene requires the interaction of NF-kappa B proteins bound to multiple regulatory elements.

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