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- Title
An evaluation of the anti-inflammatory properties of the pregnane X receptor gene isoforms PXR1 and PXR3.
- Authors
Alleyne, Jerusalem
- Abstract
The pregnane X receptor (PXR) is a nuclear receptor (NR) that primarily activates genes involved in drug metabolism. However, PXR also suppresses inflammation. This study investigated the anti-inflammatory activity of PXR1 and the minor isoform PXR3. Luciferase reporter experiments showed that like wt PXR1, PXR1 mutants and wt PXR3 that are transcriptionally inactive suppressed pro-inflammatory gene expression. This suggests that PXR uses distinct regions and by extension mechanisms to induce and repress gene induction. This study hypothesised that PXR represses inflammation via a mechanism called transrepression. One crucial feature of transrepression is conjugation with Small Ubiquitin-like Modifier (SUMO) proteins. Pull-down assays showed that both wt PXR1 and wt PXR3 are targets for conjugation with SUMO1, –2 and –3 proteins. The mutagenesis of putative SUMO conjugation sites revealed that residues K170 and K108 within PXR1 and PXR3, respectively, are important for their transrepressive activity. Collectively, these findings provide further insight into the anti-inflammatory properties of PXR.
- Subjects
PREGNANE X receptor; GENE expression; GENES
- Publication
European Journal of Inflammation, 2019, Vol 17, p1
- ISSN
1721-727X
- Publication type
Letter
- DOI
10.1177/2058739219848571