O-GlcNAc modification of PPARγ reduces its transcriptional activity

Suena Ji; Sang Yoon Park; Jürgen Roth; Hoe Suk Kim; Jin Won Cho

doi:10.1016/j.bbrc.2011.12.086

O-GlcNAc modification of PPARγ reduces its transcriptional activity

Suena Ji, Sang Yoon Park, Jürgen Roth, Hoe Suk Kim, Jin Won Cho

Research output: Contribution to journal › Article › peer-review

56 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1158-1163
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	417
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2011.12.086
Publication status	Published - 2012 Jan 27

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation (NRF) funded by the Korean Government ( 2011-0020479 to J.W.C. and 2010-0027736 to J.R.), World Class University Program (R31-2008-000-10086-0 to J.W.C. and J.R.) and partly by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD; KRF-2006-311-C00399).

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2011.12.086

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title = "O-GlcNAc modification of PPARγ reduces its transcriptional activity",

abstract = "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.",

author = "Suena Ji and Park, {Sang Yoon} and J{\"u}rgen Roth and Kim, {Hoe Suk} and Cho, {Jin Won}",

note = "Funding Information: This work was supported by the National Research Foundation (NRF) funded by the Korean Government ( 2011-0020479 to J.W.C. and 2010-0027736 to J.R.), World Class University Program (R31-2008-000-10086-0 to J.W.C. and J.R.) and partly by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD; KRF-2006-311-C00399). ",

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AU - Ji, Suena

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AU - Roth, Jürgen

AU - Kim, Hoe Suk

AU - Cho, Jin Won

N1 - Funding Information: This work was supported by the National Research Foundation (NRF) funded by the Korean Government ( 2011-0020479 to J.W.C. and 2010-0027736 to J.R.), World Class University Program (R31-2008-000-10086-0 to J.W.C. and J.R.) and partly by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD; KRF-2006-311-C00399).

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N2 - 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.

AB - 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.

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O-GlcNAc modification of PPARγ reduces its transcriptional activity

Abstract

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