IκB: a Specific Inhibitor of the NF-κB Transcription Factor

Baeuerle, Patrick A.; Baltimore, David

doi:10.1126/science.3140380

Cited by 2,104 publications

(1,277 citation statements)

References 42 publications

Supporting

Mentioning

1,244

Contrasting

Unclassified

Order By: Relevance

“…A C-terminal domain of RelA renders this heterodimer a potent transcriptional activator. The detergent deoxycholate was found to liberate kappaB DNA binding activity in the cytoplasmic extract prepared from the unstimulated cells, confirming the existence of latent NF-κB/RelA:p50 that is bound to inhibitor(s) (Baeuerle and Baltimore, 1988b), that were later identified as the three canonical or classical IκBs, IκBα, -β and -ε. These inhibitors were also shown to retain cRelcontaining dimers and regulate their activation.…”

Section: The Canonical Nf-κb Signaling Pathwaymentioning

confidence: 68%

Crosstalk via the NF-κB signaling system

Basak¹,

Hoffmann²

2008

Cytokine & Growth Factor Reviews

155

117

View full text Add to dashboard Cite

The NF-κB family of transcription factors consists of fifteen possible dimers whose activity is controlled by a family of inhibitor proteins, known as IκBs. A variety of cellular stimuli, many of them transduced by members of the TNFR superfamily, induce degradation of IκBs to activate an overlapping subset of NF-κB dimers. However, generation and stimulus-responsive activation of NF-κB dimers are intimately linked via various cross-regulatory mechanisms that allow crosstalk between different signaling pathways through the NF-κB signaling system. In this review, we summarize these mechanisms and discuss physiological and pathological consequences of crosstalk between apparently distinct inflammatory and developmental signals. We argue that a systems approach will be valuable for understanding questions of specificity and emergent properties of highly networked cellular signaling systems.

show abstract

Section: The Canonical Nf-κb Signaling Pathwaymentioning

confidence: 68%

Crosstalk via the NF-κB signaling system

Basak¹,

Hoffmann²

2008

Cytokine & Growth Factor Reviews

155

117

View full text Add to dashboard Cite

show abstract

“…Extraction of nuclear proteins and electrophoretic mobility shift assay NIH3T3 nuclear extracts were prepared as described in Baeuerle and Baltimore (1988). In brief, cells were lysed in lysis bu er containing 20 mM HEPES, 350 mM NaCl, 20% glycerol, 1% Nonidet P-40, 1 mM MgCl 2 , 0.5 mM EDTA, 0.1 mM EGTA, 0.5 mM DTT, 1 mM Pefablock, 1 mg/ml aprotinin and 1 mg/ml leupeptin.…”

Section: Western Blot Analysesmentioning

confidence: 99%

Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression

Finkenzeller

Sparacio

Technau³

et al. 1997

Oncogene

182

170

View full text Add to dashboard Cite

Stimulation of NIH3T3 cells with platelet-derived growth factor (PDGF)-BB enhances expression of vascular endothelial growth factor (VEGF), an endothelial cell-speci®c mitogen and a key mediator of tumor angiogenesis. Here, we identi®ed cis-acting VEGF promoter elements and trans-acting factors which are involved in PDGF-stimulated VEGF expression. By 5'-deletion and transient transfection analysis, a G+C-rich region at 785 to 750 of the human VEGF promoter was shown to be necessary and su cient for both PDGF inducible and basal expression. The region contains three potential recognition sites for Sp1 transcription factors, which overlap with two Egr-1 sites. Mutations that abolish the ability of Sp1 to interact with the VEGF promoter element also abrogate expression induced by PDGF. Mutations of the potential Egr-1 binding sites did not a ect PDGF responsiveness. Gel shift and antibody supershift analyses showed that Sp1 and Sp3 interact constitutively with the VEGF promoter element. Our data strongly suggest that enhanced VEGF gene expression in PDGF-induced NIH3T3 cells is mediated by Sp1 and/or Sp3 transcription factors bound to the 785 to 750 promoter region of the VEGF gene.

show abstract

“…In unstimulated cells, NFkB is localized in the cytoplasm as an inactive complex composed of a transcriptionally active dimer associated with the inhibitory protein IkB. 3 Upon stimulation, IkB becomes phosphorylated and degraded, unmasking the nuclear localization signal of NFkB. This will permit the active transcription factor to translocate to the nucleus, bind to the kB DNA motifs and activate target genes.…”

Section: Introductionmentioning

confidence: 99%

Cellular delivery of a double-stranded oligonucleotide

et al. 2004

View full text Add to dashboard Cite

The activation of nuclear factor kB (NFkB) is a key event in immune and inflammatory responses. In this study, a cellpenetrating transport peptide, transportan (TP) or its shorter analogue TP 10, was used to facilitate the cellular uptake of an NFkB decoy. Peptide nucleic acid (PNA) hexamer or nonamer was linked to the transport peptide by a disulfide bond. NFkB decoy oligonucleotide consisted of a doublestranded consensus sequence corresponding to the kB site localized in the IL-6 gene promoter, 5 0 -GGGACTTTCCC-3 0 , with a single-stranded protruding 3 0 -terminal sequence complementary to the PNA sequence was hybridized to the transport peptide-PNA construct. The ability of the transport peptide-PNA-NFkB decoy complex to block the effect of interleukin (IL)-1b-induced NFkB activation and IL-6 gene expression was analyzed by electrophoretic mobility shift assay and reverse transcriptase-polymerase chain reaction in rat Rinm5F insulinoma cells. Preincubation with transport peptide-PNA-NFkB decoy (1 mM, 1 h) blocked IL-1b-induced NFkB-binding activity and significantly reduced the IL-6 mRNA expression. The same concentration of NFkB decoy in the absence of transport peptide-PNA had no effect even after longer incubations. Our results showed that binding of the oligonucleotide NFkB decoy to the nonamer PNA sequence resulted in a stable complex that was efficiently translocated across the plasma membrane.

show abstract

IκB: a Specific Inhibitor of the NF-κB Transcription Factor

Cited by 2,104 publications

References 42 publications

Crosstalk via the NF-κB signaling system

Crosstalk via the NF-κB signaling system

Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression

Cellular delivery of a double-stranded oligonucleotide

Contact Info

Product

Resources

About