SUMOylation of Human Peroxisome Proliferator-activated Receptor ?? Inhibits Its Trans-activity through the Recruitment of the Nuclear Corepressor NCoR |
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| Authors: | Benoit Pourcet In??s Pineda-Torra Bruno Derudas Bart Staels and Corine Glineur |
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| Institution: | From the ‡Université Lille Nord de France, ;§Inserm, U545, and ;¶UDSL, F-59000 Lille, France, ;the ‖Institut Pasteur de Lille, F-59019 Lille, France, and ;the **Division of Medicine, University College of London, London WC1 E6JJ, United Kingdom |
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| Abstract: | The nuclear receptor peroxisome proliferator-activated receptor α (PPARα) is a key regulator of genes implicated in lipid homeostasis and inflammation. PPARα 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, PPARα activity is regulated by post-translational modifications such as phosphorylation and ubiquitination. In this report, we demonstrate that hPPARα 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 hPPARα. Finally, our results demonstrate that SUMO-1 modification of hPPARα down-regulates its trans-activity through the specific recruitment of corepressor NCoR but not SMRT leading to the differential expression of a subset of PPARα target genes. In conclusion, hPPARα SUMOylation on lysine 185 down-regulates its trans-activity through the selective recruitment of NCoR. |
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