Review Article

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

Figure 3

Molecular mechanisms of PPAR transrepression pathways. (a-b) Ligand-activated PPAR (α or γ) inhibits the activities of AP-1 and NF-κB through direct interactions with the c-Jun subunit and the p65 subunit, respectively. (c) On ligand binding, PPARγ is sumoylated and blocks ubiquitin-dependent proteasomal degradation of the NCoR corepressor complexes at NF-κB-binding sites. The presence of the corepressor complexes prevents the recruitment of transcriptionally active NF-κB, leading to inhibition of inflammatory gene expression.