| First Author | Ohshima T | Year | 2004 |
| Journal | J Biol Chem | Volume | 279 |
| Issue | 28 | Pages | 29551-7 |
| PubMed ID | 15123625 | Mgi Jnum | J:262338 |
| Mgi Id | MGI:6162273 | Doi | 10.1074/jbc.M403866200 |
| Citation | Ohshima T, et al. (2004) Transcriptional activity of peroxisome proliferator-activated receptor gamma is modulated by SUMO-1 modification. J Biol Chem 279(28):29551-7 |
| abstractText | Covalent modification of many transcription factors with SUMO-1 is emerging as a key role of trans-activational regulation. Here, we demonstrate that peroxisome proliferator-activated receptor (PPAR) gamma, which is a ligand-activated nuclear receptor, is modified by SUMO-1. Sumoylation of PPARgamma mainly occurs at a lysine residue within the activation function 1 domain. Furthermore, we show that the PIAS family proteins, PIAS1 and PIASxbeta, function as E3 ligases (ubiquitin-protein isopeptide ligase) for PPARgamma. PPARgamma interacts directly with PIASxbeta in a ligand-independent manner. Analysis using a PPARgamma mutant with a disrupted sumoylation site shows that modification of PPARgamma by SUMO-1 represses its transcriptional activity. Interestingly, PIASxbeta and Ubc9 enhance the transcriptional activity of PPARgamma independent of PPARgamma sumoylation. Furthermore, PPARgamma ligand-induced apoptosis in a human hepatoblastoma cell line, HepG2, is significantly enhanced by ectopic production of the sumoylation-mutant PPARgamma. These results suggest that the PPARgamma-dependent transactivation pathway seems to be modulated by SUMO-1 modification and may serve as a novel target for apoptosis-induction therapy in cancer cells. |
