Yonsei Med J.  2013 May;54(3):545-559. 10.3349/ymj.2013.54.3.545.

Modulation of the Transcriptional Activity of Peroxisome Proliferator-Activated Receptor Gamma by Protein-Protein Interactions and Post-Translational Modifications

• Kim TH
• Kim MY
• Jo SH
• Park JM
• Ahn YH

• KMID: 1727863
• DOI: http://doi.org/10.3349/ymj.2013.54.3.545

Abstract

Peroxisome proliferator-activated receptor gamma (PPARgamma) belongs to a nuclear receptor superfamily; members of which play key roles in the control of body metabolism principally by acting on adipose tissue. Ligands of PPARgamma, such as thiazolidinediones, are widely used in the treatment of metabolic syndromes and type 2 diabetes mellitus (T2DM). Although these drugs have potential benefits in the treatment of T2DM, they also cause unwanted side effects. Thus, understanding the molecular mechanisms governing the transcriptional activity of PPARgamma is of prime importance in the development of new selective drugs or drugs with fewer side effects. Recent advancements in molecular biology have made it possible to obtain a deeper understanding of the role of PPARgamma in body homeostasis. The transcriptional activity of PPARgamma is subject to regulation either by interacting proteins or by modification of the protein itself. New interacting partners of PPARgamma with new functions are being unveiled. In addition, post-translational modification by various cellular signals contributes to fine-tuning of the transcriptional activities of PPARgamma. In this review, we will summarize recent advancements in our understanding of the post-translational modifications of, and proteins interacting with, PPARgamma, both of which affect its transcriptional activities in relation to adipogenesis.

Keyword

PPARgamma; coregulator; post-translational modifications; transcriptional activity; adipogenesis; metabolic syndrome

MeSH Terms

Gene Expression Regulation
Homeostasis
*Models, Genetic
PPAR gamma/genetics/metabolism/*physiology
*Protein Processing, Post-Translational
Sumoylation
Transcription Factors/metabolism/physiology
Ubiquitination
PPAR gamma
Transcription Factors

Figure

• 

  Fig. 1 Modulation of PPARγ activity by phosphorylation. Positions of phosphorylation sites in PPARγ and the implicated signaling pathways are indicated. Ser112 phosphorylation by growth factors, cytokines, and stress signals are related to decreased PPARγ activity, whereas phosphorylation by Cdk7 and Cdk9 is related to increased PPARγ activity. Obesity or high-fat diet-mediated phosphorylation of PPARγ at Ser273 is related to decreased insulin sensitivity. AF-1 and 2, activation function 1 and 2, respectively; Cdk5, 7 and 9, cyclin-dependent kinase 5, 7 and 9, respectively; DBD, DNA binding domain; Dok1, downstream of tyrosine kinase-1; ERK1/2, extracellular signal-regulated kinase 1/2; HFD, high fat diet; JNK, c-Jun N-terminal kinase; LBD, ligand binding domain; MAPK, mitogen-activated protein kinase; p38, p38 MAP kinase; Rosi, rosiglitasone; PPARγ, peroxisome proliferator-activated receptor gamma.

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