Review Article

A Retrospective on Nuclear Receptor Regulation of Inflammation: Lessons from GR and PPARs

Figure 2

Molecular mechanisms of GR transrepression of AP-1 and NF-κB. (a) Ligand-activated GR is tethered to AP-1 and recruits transcriptional mediators/intermediary factor 2 (TIF-2) to inhibit transcription of AP-1 target genes. (b) Ligand-activated GR bound to NF-κB interferes with recruitment of NF-κB Ser2 CTD kinase, positive transcription elongation factor b (P-TEFb), which is required for the transcription of proinflammatory genes. (c) Ligand-activated GR induces synthesis of IκBα, thereby blocking NF-κB nuclear translocation.