Article (Scientific journals)
RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100.
Derudder, Emmanuel; Dejardin, Emmanuel; Pritchard, Linda L. et al.
2003In Journal of Biological Chemistry, 278 (26), p. 23278-84
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Keywords :
Active Transport, Cell Nucleus; Animals; DNA/metabolism; Dimerization; Fibroblasts/metabolism; Gene Expression Regulation; I-kappa B Kinase; I-kappa B Proteins/metabolism; Lymphotoxin beta Receptor; Mice; NF-kappa B/metabolism; NF-kappa B p50 Subunit; Nuclear Proteins/metabolism/physiology; Protein Binding; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins/antagonists & inhibitors/metabolism; Receptors, Tumor Necrosis Factor/metabolism/physiology; Transcription Factor RelB; Transcription Factors/antagonists & inhibitors/metabolism; Tumor Necrosis Factor-alpha/physiology
Abstract :
[en] Tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin-beta receptor (LTbetaR) signaling both play important roles in inflammatory and immune responses through activation of NF-kappaB. Using various deficient mouse embryonic fibroblast cells, we have compared the signaling pathways leading to NF-kappaB induction in response to TNF-alpha and LTbetaR activation. We demonstrate that LTbetaR ligation induces not only RelA/p50 dimers but also RelB/p50 dimers, whereas TNF-alpha induces only RelA/p50 dimers. LTbetaR-induced binding of RelB/p50 requires processing of p100 that is mediated by IKKalpha but is independent of IKKbeta, NEMO/IKKgamma, and RelA. Moreover, we show that RelB, p50, and p100 can associate in the same complex and that TNF-alpha but not LTbeta signaling increases the association of p100 with RelB/p50 dimers in the nucleus, leading to the specific inhibition of RelB DNA binding. These results suggest that the alternative NF-kappaB pathway based on p100 processing may account not only for the activation of RelB/p52 dimers but also for that of RelB/p50 dimers and that p100 regulates the binding activity of RelB/p50 dimers via at least two distinct mechanisms depending on the signaling pathway involved.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Derudder, Emmanuel
Dejardin, Emmanuel ;  Université de Liège - ULiège > GIGA-R : Labo of Molecular Immunol. and Signal Transduction
Pritchard, Linda L.
Green, Douglas R.
Korner, Marie
Baud, Veronique
Language :
English
Title :
RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100.
Publication date :
2003
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, United States - Maryland
Volume :
278
Issue :
26
Pages :
23278-84
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 05 March 2015

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