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Control of Peroxisome Proliferator-Activated Receptor γ2 Stability and Activity by SUMOylation
Article first published online: 6 SEP 2012
2004 North American Association for the Study of Obesity (NAASO)
Volume 12, Issue 6, pages 921–928, June 2004
How to Cite
Floyd, Z. E. and Stephens, J. M. (2004), Control of Peroxisome Proliferator-Activated Receptor γ2 Stability and Activity by SUMOylation. Obesity Research, 12: 921–928. doi: 10.1038/oby.2004.112
- Issue published online: 6 SEP 2012
- Article first published online: 6 SEP 2012
- Received for review February 06, 2004; Accepted in final form March 25, 2004
- fat cells;
- peroxisome proliferator-activated receptor γ;
- small ubiquitin-related modifier-1;
Objective: To determine whether small ubiquitin-related modifier (SUMO)ylation of lysine 107 plays a role in regulating the activity of peroxisome proliferator-activated receptor γ (PPARγ).
Research Methods and Procedures: Transient expression of wild-type and K107R-PPARγ2 in the NIH 3T3 fibroblast cell line was carried out in conjunction with half-life studies, luciferase activity assays, and indirect immunofluorescence localization studies. Additional in vitro analysis was carried out using recombinant SUMOylation pathway proteins along with in vitro transcribed and translated wild-type or K107R-PPARγ2 to examine the SUMO-1 modification state of wild-type and SUMO-deficient K107R-PPARγ2.
Results: While examining PPARγ2 for potential ubiquitylation sites, we identified a strong consensus site for SUMO modification that contains lysine 107. In vitro, SUMOylation studies showed that lysine 107 of PPARγ2 is a major SUMOylation site and that at least one other SUMOylation site is present in PPARγ. In addition, our results demonstrated that SUMO-1 affects PPARγ stability and transcriptional activity but not the nuclear localization of PPARγ.
Discussion: These results indicated that SUMOylation plays a role in regulating PPARγ, both indirectly and directly by modification of lysine 107. Because PPARγ is regulated in numerous animal models of obesity, understanding the covalent modifications of PPARγ may enhance our understanding of the metabolic syndrome.