An evaluation of the anti-inflammatory properties of the pregnane X receptor gene isoforms PXR1 and PXR3
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...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2019-05-01
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| Series: | European Journal of Inflammation |
| Online Access: | https://doi.org/10.1177/2058739219848571 |
| _version_ | 1819066982445613056 |
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| author | Jerusalem Alleyne |
| author_facet | Jerusalem Alleyne |
| author_sort | Jerusalem Alleyne |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T16:11:00Z |
| format | Article |
| id | doaj.art-f071e2da70894146a5cdad57a1e810af |
| institution | Directory Open Access Journal |
| issn | 2058-7392 |
| language | English |
| last_indexed | 2024-12-21T16:11:00Z |
| publishDate | 2019-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | European Journal of Inflammation |
| spelling | doaj.art-f071e2da70894146a5cdad57a1e810af2022-12-21T18:57:48ZengSAGE PublishingEuropean Journal of Inflammation2058-73922019-05-011710.1177/2058739219848571An evaluation of the anti-inflammatory properties of the pregnane X receptor gene isoforms PXR1 and PXR3Jerusalem AlleyneThe 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.https://doi.org/10.1177/2058739219848571 |
| spellingShingle | Jerusalem Alleyne An evaluation of the anti-inflammatory properties of the pregnane X receptor gene isoforms PXR1 and PXR3 European Journal of Inflammation |
| title | An evaluation of the anti-inflammatory properties of the pregnane X receptor gene isoforms PXR1 and PXR3 |
| title_full | An evaluation of the anti-inflammatory properties of the pregnane X receptor gene isoforms PXR1 and PXR3 |
| title_fullStr | An evaluation of the anti-inflammatory properties of the pregnane X receptor gene isoforms PXR1 and PXR3 |
| title_full_unstemmed | An evaluation of the anti-inflammatory properties of the pregnane X receptor gene isoforms PXR1 and PXR3 |
| title_short | An evaluation of the anti-inflammatory properties of the pregnane X receptor gene isoforms PXR1 and PXR3 |
| title_sort | evaluation of the anti inflammatory properties of the pregnane x receptor gene isoforms pxr1 and pxr3 |
| url | https://doi.org/10.1177/2058739219848571 |
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