Details

Autor(en) / Beteiligte

• Marienfeld, Ralf
• May, Michael J.
• Berberich, Ingolf
• Serfling, Edgar
• Ghosh, Sankar
• Neumann, Manfred

Titel

RelB Forms Transcriptionally Inactive Complexes with RelA/p65

Ist Teil von

• The Journal of biological chemistry, 2003-05, Vol.278 (22), p.19852-19860

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2003

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• RelB is an unusual member of the NF-κB transcription factor family that acts as both a transcriptional activator as well as a repressor of NF-κB-dependent gene expression. Although RelB promotes gene expression when it associates with p50/NF-κB1 or p52/NF-κB2, the precise molecular mechanisms through which it represses NF-κB remain unclear. To examine this inhibitory function in more detail, we employed reporter gene assays and found that RelB represses at the level of RelA. Furthermore, electrophoretic mobility shift analysis revealed that in vitro translated RelB impaired the DNA binding activity of RelA and that overexpressed RelB significantly reduced tumor necrosis factor-α-induced RelA activity in murine embryonic fibroblasts. Intriguingly, this inhibitory effect was due to the formation of RelA·RelB heterodimers that were unable to bind to κB sites in vitro strongly suggesting that these newly described NF-κB dimers cannot bind DNA. Expression pattern analysis revealed that RelA·RelB heterodimers appeared at relatively low levels in both lymphoid and non-lymphoid cells. However, the presence of these complexes increased following stimulation with phorbolesters or lipopolysaccharide or by overexpression of constitutively active IKKβ. Functional characterization of RelA·RelB heterodimers in NIH3T3 murine embryonic fibroblasts revealed that they are not regulated by IκB proteins and are located in both the cytoplasm and the nucleus. Taken together, our findings demonstrate that sequestration of RelA in transcriptionally inactive RelA·RelB complexes provides a molecular mechanism that may explain the repressive role of RelB on NF-κB-dependent gene expression.