| First Author | Pourcet B | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 9 | Pages | 5983-92 |
| PubMed ID | 19955185 | Mgi Jnum | J:168276 |
| Mgi Id | MGI:4887534 | Doi | 10.1074/jbc.M109.078311 |
| Citation | Pourcet B, et al. (2010) SUMOylation of human peroxisome proliferator-activated receptor alpha inhibits its trans-activity through the recruitment of the nuclear corepressor NCoR. J Biol Chem 285(9):5983-92 |
| abstractText | The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) is a key regulator of genes implicated in lipid homeostasis and inflammation. PPARalpha trans-activity is enhanced by recruitment of coactivators such as SRC1 and CBP/p300 and is inhibited by binding of corepressors such as NCoR and SMRT. In addition to ligand binding, PPARalpha activity is regulated by post-translational modifications such as phosphorylation and ubiquitination. In this report, we demonstrate that hPPARalpha is SUMOylated by SUMO-1 on lysine 185 in the hinge region. The E2-conjugating enzyme Ubc9 and the SUMO E3- ligase PIASy are implicated in this process. In addition, ligand treatment decreases the SUMOylation rate of hPPARalpha. Finally, our results demonstrate that SUMO-1 modification of hPPARalpha down-regulates its trans-activity through the specific recruitment of corepressor NCoR but not SMRT leading to the differential expression of a subset of PPARalpha target genes. In conclusion, hPPARalpha SUMOylation on lysine 185 down-regulates its trans-activity through the selective recruitment of NCoR. |
