Table 1.
Summary of ubiquitin and SUMO modification of PPARs and the resulting effects on transcription in the presence or absence of ligand
| Nuclear Receptor | Post-translational Modification | Ubiquitin/SUMO Ligase (E3) Identified | Modification Type | Transcriptional Affect | Effect of Ligand | Cell type | References |
|---|---|---|---|---|---|---|---|
| PPARα | Ubiquitination | MDM2 | Polyubiquitination | MDM2-to-PPARα ratio < 0.5: Activation MDM2-to-PPARα ratio ≥ 1.0: Inhibition | Wy14643 is required for MDM2-dependent modulation of PPARα activity | Rat hepatoma | (30) |
| Inhibition of PPARα activity by promoting its degradation | Wy14643 blocks PPARα polyubiquitination | HepG2 | (11, 12, 36) | ||||
| SUMOylation | PIASy | SUMO-1, K185 | Inhibition of PPARα activity by recruiting NCoR corepressor | GW-7647 blocks PPARα monoSUMOylation | COS-7; human hepatoma | (66) | |
| SUMO-2/3, K358 | Not determined | Not determined | NIH3T3; HepG2 | ||||
| SUMO-1, K358 | Inhibition of PPARα activity by recruiting GA-binding protein and histone deacetylases | WY-14643 enhances PPARα monoSUMOylation | NIH3T3; HepG2 | (47) | |||
| PPARβ (also known as PPARδ) | Ubiquitination | Not determined | Polyubiquitination | Inhibition of PPARβ activity by promoting its degradation | PPARβ low and high: GW-501516, L-165041, and cPGI2block PPARβ polyubiquitination | U2OS; human lung cell lines | (28) |
| PPARβ low: GW501516 does not affect PPARβ polyubiquitination | HEK293; mouse fibroblasts | (68) | |||||
| PPARβ high: GW-501516 blocks PPARβ polyubiquitination | |||||||
| PPARγ1/2 | Ubiquitination | Not determined | Polyubiquitination | Inhibition of PPARγ1 activity by promoting its degradation | Thiazolidinediones enhance PPARγ polyubiquitination | Differentiated adipocytes | (34) |
| SUMOylation | PIAS1 & PIASxβ SUMOylates SENP2 deSUMOylates | SUMO-1, K77/K107 SUMO-1, K365/K395 | Inhibition of PPARγ1 activity Inhibition of PPARγ1 activity by recruiting NCoR corepressor | Rosiglitazone enhances PPARγ1 SUMOylation Rosiglitazone has no affect on PPARγ1 deSUMOylation (C2C12) | HEK293; HepG2; NIH3T3; vascular smooth muscle cells; in vivorat cartiod artery; C2C12 | (15, 24, 49, 60, 64, 75, 89) | |
| Rosiglitazone enhances PPARγ1 SUMOylation | Mouse macrophage |
See main text for definition of abbreviations.