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Differential activation of nuclear factor‐κB by tumour necrosis factor receptor subtypes. TNFR1 predominates whereas TNFR2 activates transcription poorly
Author(s) -
McFarlane Shona M,
Pashmi Ghazaleh,
Connell Michelle C,
Littlejohn Alison F,
Tucker Steven J,
Vandenabeele Peter,
MacEwan David J
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02450-x
Subject(s) - tumor necrosis factor receptor 1 , transcription factor , tumor necrosis factor alpha , electrophoretic mobility shift assay , nf κb , nfkb1 , microbiology and biotechnology , chemistry , receptor , signal transduction , biology , immunology , tumor necrosis factor receptor , biochemistry , gene
Tumour necrosis factor‐α (TNF‐α) signals though two receptors, TNFR1 and TNFR2. TNFR1 has a role in cytotoxicity, whereas TNFR2 regulates death responses or proliferation. TNF activates pro‐inflammatory transcription factor nuclear factor‐κB (NF‐κB) by uncertain signalling mechanisms. Here we report the contribution of each TNFR towards the NF‐κB activation processes. In human cells expressing endogenous or exogenous TNFR2, in addition to TNFR1, we found both TNFRs capable of activating NF‐κB, as measured by IκBα (inhibitor of NF‐κB) degradation, electrophoretic mobility shift assay and NF‐κB gene reporter assays. TNFR2 activation did not degrade IκBβ. However, TNF‐effects on NF‐κB activation occurred predominantly through TNFR1, with TNFR2 activating the transcription factor poorly.