First Author | Ji S | Year | 2012 |
Journal | Biochem Biophys Res Commun | Volume | 417 |
Issue | 4 | Pages | 1158-63 |
PubMed ID | 22226965 | Mgi Jnum | J:181224 |
Mgi Id | MGI:5309089 | Doi | 10.1016/j.bbrc.2011.12.086 |
Citation | Ji S, et al. (2012) O-GlcNAc modification of PPARgamma reduces its transcriptional activity. Biochem Biophys Res Commun 417(4):1158-63 |
abstractText | The peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, is a key regulator of adipogenesis and is important for the homeostasis of the adipose tissue. The beta-O-linked N-acetylglucosamine (O-GlcNAc) modification, a posttranslational modification on various nuclear and cytoplasmic proteins, is involved in the regulation of protein function. Here, we report that PPARgamma is modified by O-GlcNAc in 3T3-L1 adipocytes. Mass spectrometric analysis and mutant studies revealed that the threonine 54 of the N-terminal AF-1 domain of PPARgamma is the major O-GlcNAc site. Transcriptional activity of wild type PPARgamma was decreased 30% by treatment with the specific O-GlcNAcase (OGA) inhibitor, but the T54A mutant of PPARgamma did not respond to inhibitor treatment. In 3T3-L1 cells, an increase in O-GlcNAc modification by OGA inhibitor reduced PPARgamma transcriptional activity and terminal adipocyte differentiation. Our results suggest that the O-GlcNAc state of PPARgamma influences its transcriptional activity and is involved in adipocyte differentiation. |