O-GlcNAc modification of PPARγ reduces its transcriptional activity.
The peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, is a key regulator of adipogenesis and is important for the homeostasis of the adipose tissue. The β-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 PPARγ 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 PPARγ is the major O-GlcNAc site. Transcriptional activity of wild type PPARγ was decreased 30% by treatment with the specific O-GlcNAcase (OGA) inhibitor, but the T54A mutant of PPARγ did not respond to inhibitor treatment. In 3T3-L1 cells, an increase in O-GlcNAc modification by OGA inhibitor reduced PPARγ transcriptional activity and terminal adipocyte differentiation. Our results suggest that the O-GlcNAc state of PPARγ influences its transcriptional activity and is involved in adipocyte differentiation.
Department of Biology, Yonsei University, Seoul 120-749, Republic of Korea.
Suena
S
Ji
Sang Yoon
SY
Park
Jürgen
J
Roth
Hoe Suk
HS
Kim
Jin Won
JW
Cho
D000117:Acetylglucosamine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D014158:Transcription, Genetic
C555050:1,2-dideoxy-2'-propylglucopyranoso(2,1-d)-delta 2'-thiazoline; D019086:Bridged Bicyclo Compounds, Heterocyclic; D047495:PPAR gamma; D000117:Acetylglucosamine