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Lymphotoxin and lipopolysaccharide induce NF‐κB‐p52 generation by a co‐translational mechanism
Author(s) -
Mordmüller Benjamin,
Krappmann Daniel,
Esen Meral,
Wegener Elmar,
Scheidereit Claus
Publication year - 2003
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.embor710
Subject(s) - iκb kinase , lymphotoxin , microbiology and biotechnology , tumor necrosis factor alpha , traf2 , phosphorylation , signal transduction , kinase , nf κb , lymphotoxin alpha , biology , chemistry , endocrinology , tumor necrosis factor receptor
The ‘classical’ NF‐κB activation pathway proceeds via IκB kinase (IKK)‐β/γ‐mediated phosphorylation, induced ubiquitination and the degradation of small IκBs. An alternative, NF‐κB‐inducing kinase and IKK‐α‐dependent pathway, which stimulates the processing of NF‐κB2/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 β (LT‐β) receptor agonists or lipopolysaccharide (LPS), but not with interleukin‐1β, tumour necrosis factor‐α 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‐β receptor agonists and LPS induce NF‐κB/p100 processing to p52 at the level of the ribosome.