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| Item Type: | Article |
|---|---|
| Title: | Lymphotoxin and lipopolysaccharide induce NF-κB-p52 generation by a co-translational mechanism |
| Creators Name: | Mordmueller, B., Krappmann, D., Esen, M., Wegener, E. and Scheidereit, C. |
| Abstract: | The 'classical' NF-{kappa}B activation pathway proceeds via IκB kinase (IKK)-{beta}/{gamma}-mediated phosphorylation, induced ubiquitination and the degradation of small I{kappa}Bs. An alternative, NF-{kappa}B-inducing kinase and IKK-{alpha}-dependent pathway, which stimulates the processing of NF-{kappa}B2/p100, has recently been suggested. However, no physiological stimulus has been shown to trigger the activation of this pathway. Here we demonstrate that persistent stimulation with lymphotoxin {beta} (LT-{beta}) receptor agonists or lipopolysaccharide (LPS), but not with interleukin-1{beta}, tumour necrosis factor-{alpha} or 12-O-tetradecanoylphorbol-13-acetate, induces the generation of p52 DNA-binding complexes by activating the processing of the p100 precursor. Induction of p52 DNA-binding activity is delayed in comparison with p50/p65 complexes and depends on de novo protein synthesis. p100 is constitutively and inducibly polyubiquitinated, and both ubiquitination and p52 generation are coupled to continuing p100 translation. Thus, both LT-{beta} receptor agonists and LPS induce NF-{kappa}B/p100 processing to p52 at the level of the ribosome. |
| Keywords: | Adenocarcinoma, B-Lymphocytes, Breast Neoplasms, Cultured Tumor Cells, Dendritic Cells, DNA, Enzyme Activation, Hela Cells, I-kappa B Proteins, Interleukin-1, Lipopolysaccharides, Lymphotoxin Beta Receptor, Lymphotoxin-Alpha, Lymphotoxin-Beta, Membrane Proteins, NF-{kappa} B, NF-{kappa} B p52 Subunit, Post-Translational Protein Processing, Protein Binding, Protein Precursors, Recombinant Fusion Proteins, Ribosomes, Sequence Deletion, Signal Transducing Adaptor Proteins, Tetradecanoylphorbol Acetate, Trans-Activators, Transcription Factors, Tumor Necrosis Factor Ligand Superfamily Member 14, Tumor Necrosis Factor Receptors, Tumor Necrosis Factor-Alpha, Ubiquitin |
| Source: | EMBO Reports |
| ISSN: | 1469-221X |
| Publisher: | Nature Publishing Group |
| Volume: | 4 |
| Number: | 1 |
| Page Range: | 82-87 |
| Date: | 1 January 2003 |
| Official Publication: | https://doi.org/10.1038/sj.embor.embor710 |
| PubMed: | View item in PubMed |
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