[Negative cross-talk between nuclear receptors and transcription factors: implications in inflammation and...

Nuclear receptors are transcription factors mediating a signal pathway that triggers the cell into differentiation. By contrast, membrane receptors mediate a proliferation signal pathway via a phosphorylation cascade that activates transcription factors such as NF-kappa B and AP-1 complex. To allow efficient cellular integration of these contradictory signals, transcription factors mutually interact and modulate their transcription activity. Although often synergistic, these interactions can also be negative. They then result from various mechanisms acting either at the transcriptional level (competitive binding to DNA or to a common limitant cofactor...) or upstream DNA binding (inhibition of DNA binding, inhibition of phosphorylation...). Whatever the precise mechanisms, these negative interactions are significant in vivo. For instance, glucocorticoid and PPAR receptors repress the transcription activity of the pro-inflammatory factor NF-kappa B. This partly explains the anti-inflammatory effects of their respective ligands (glucocorticoids and fibrates). Likewise, interactions between nuclear receptors and AP-1 complex are likely to participate to the anti-oncogenic activity of glucocorticoids and retinoic acid.