PMID- 12709443
OWN - NLM
STAT- MEDLINE
DCOM- 20030820
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 26
DP  - 2003 Jun 27
TI  - RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and 
      lymphotoxin-beta receptor activation: critical roles for p100.
PG  - 23278-84
AB  - 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.
FAU - Derudder, Emmanuel
AU  - Derudder E
AD  - Laboratoire Oncogenese, Differenciation et Transduction du Signal, CNRS UPR 9079, 
      Institut Andre Lwoff, 7 rue Guy Moquet, 94801 Villejuif, France.
FAU - Dejardin, Emmanuel
AU  - Dejardin E
FAU - Pritchard, Linda L
AU  - Pritchard LL
FAU - Green, Douglas R
AU  - Green DR
FAU - Korner, Marie
AU  - Korner M
FAU - Baud, Veronique
AU  - Baud V
LA  - eng
GR  - AI44828/AI/NIAID NIH HHS/United States
GR  - CA69381/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030421
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Ltbr protein, mouse)
RN  - 0 (Lymphotoxin beta Receptor)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Relb protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 147337-75-5 (Transcription Factor RelB)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (Chuk protein, mouse)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (Ikbkb protein, mouse)
RN  - EC 2.7.11.10 (Ikbke protein, mouse)
RN  - EC 3.1.- (Endonucleases)
RN  - EC 3.1.- (Snd1 protein, mouse)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Animals
MH  - DNA/metabolism
MH  - Dimerization
MH  - Endonucleases
MH  - Fibroblasts/metabolism
MH  - Gene Expression Regulation
MH  - I-kappa B Kinase
MH  - I-kappa B Proteins/metabolism
MH  - Lymphotoxin beta Receptor
MH  - Mice
MH  - NF-kappa B/*metabolism
MH  - NF-kappa B p50 Subunit
MH  - Nuclear Proteins/metabolism/*physiology
MH  - Protein Binding
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/antagonists & inhibitors/*metabolism
MH  - Receptors, Tumor Necrosis Factor/*metabolism/physiology
MH  - Transcription Factor RelB
MH  - Transcription Factors/antagonists & inhibitors/*metabolism
MH  - Tumor Necrosis Factor-alpha/*physiology
EDAT- 2003/04/24 05:00
MHDA- 2003/08/21 05:00
CRDT- 2003/04/24 05:00
PHST- 2003/04/24 05:00 [pubmed]
PHST- 2003/08/21 05:00 [medline]
PHST- 2003/04/24 05:00 [entrez]
AID - S0021-9258(20)86124-9 [pii]
AID - 10.1074/jbc.M300106200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Jun 27;278(26):23278-84. doi: 10.1074/jbc.M300106200. Epub 2003 
      Apr 21.