PMID: 22226965

 

    Legend: Gene, Sites

Title : O-GlcNAc modification of PPARγ reduces its transcriptional activity

Abstract :

1. 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
2. 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
3. Here, we report that PPARγ is modified by O-GlcNAc in 3T3-L1 adipocytes
4. 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
5. 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
6. In 3T3-L1 cells, an increase in O-GlcNAc modification by OGA inhibitor reduced PPARγ transcriptional activity and terminal adipocyte differentiation
7. Our results suggest that the O-GlcNAc state of PPARγ influences its transcriptional activity and is involved in adipocyte differentiation

Output (sent_index, trigger, protein, sugar, site):

• 0. PPARγ, , PPARγ , O-GlcNAc modification, -
• 3. modified, , PPARγ , O-GlcNAc, -
• 4. AF-1, , N-terminal AF-1, the major O-GlcNAc site, -
• 4. N-terminal, , N-terminal AF-1, the major O-GlcNAc site, -
• 4. PPARγ, , PPARγ , the major O-GlcNAc site, -
• 4. threonine, , -, the major O-GlcNAc site, threonine 54
• 7. PPARγ, , PPARγ , the O-GlcNAc state, -

Output(Part-Of) (sent_index, protein, site):

• 4. N-terminal AF-1, domain
• 4. PPARγ , domain

*Output_Site_Fusion* (sent_index, protein, sugar, site):

• 4. PPARγ , the major O-GlcNAc site, threonine 54

 

Protein	NCBI ID	SENTENCE INDEX
O-GlcNAcase	76055	5
OGA	76055	5,6
peroxisome proliferator-activated receptor γ	19016	1
PPARγ	19016	0,3,4,5,6,7
PPARγ)	19016	1