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Lymphotoxin and lipopolysaccharide induce NF-κB-p52 generation by a co-translational mechanism

Item Type:Article
Title:Lymphotoxin and lipopolysaccharide induce NF-κB-p52 generation by a co-translational mechanism
Creators Name:Mordmueller, B. and Krappmann, D. and Esen, M. and 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
Publisher:Nature Publishing Group
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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