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Publication : O-GlcNAc modification of PPARĪ³ reduces its transcriptional activity.

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.
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