Pparg:Rxra heterodimer binds to fatty acids

Stable Identifier
R-MMU-556760
Type
Reaction [binding]
Species
Mus musculus
Compartment
nucleoplasm
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Pparg:Rxra heterodimer binds to fatty acids
PPARG can be activated in cell cultures by adding ligands such as polyunsaturated fatty acids and certain prostanoids (prostaglandins). Endogenous fatty acids are relatively poor activators. Which ligands are most responsible for PPARG activation in the body has not yet been established. Generally, oxidized fatty acids such as 9(S')-hydroxyoctadeca-10,12-dienoic acid (9(S')-HODE) and 13(S')-HODE are more effective activators than are endogenous fatty acids. The thiazolidinedione (TZD) class of antidiabetic drugs are agonist ligands for PPARG (Lambe and Tugwood 1996).
FABP4 delivers ligands to PPARG directly. Binding of activator ligands to PPARG causes loss of corepressors such as SMRT/NCoR2, NCoR1, and HDAC3 and gain of interactions with the basal transcription machinery (Yoo et al. 2006). The TRAP220/MED1/DRIP205 subunit of the TRAP/Mediator (DRIP) complex binds directly to the LXXLL motif of PPARG and TRAP/Mediator is necessary for full transcriptional activation of target genes (Ge et al. 2008). PPARG also interacts with the MED14 subunit of the Mediator complex (Grontved et al. 2010).
Other coactivators, including NCOA1/SRC-1, NCOA2/TIF2/GRIP1, CBP, HAT/p300, and PRIP, interact with PPARG in a ligand-dependent way and enhance transcription (Gellman et al. 1999, Wallberg et al. 2003, Yang et al. 2000, Ge et al. 2002, Puigserver et al. 1999, Bugge et al. 2009, Steger et al. 2010).
The target genes of PPARG encode proteins involved in adipocyte differentiation (PGAR/ANGPTL4, PLIN, and aP2/FABP4), carbohydrate metabolism (PEPCK-C), and fatty acid transport (FAT/CD36, LPL).
Literature References
PubMed ID Title Journal Year
8001151 Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor

Tontonoz, P, Hu, E, Spiegelman, BM

Cell 1994
10558993 Activation of PPARgamma coactivator-1 through transcription factor docking

Puigserver, P, Adelmant, G, Wu, Z, Fan, M, Xu, J, O'Malley, B, Spiegelman, BM

Science 1999
20478996 Propagation of adipogenic signals through an epigenomic transition state

Steger, DJ, Grant, GR, Schupp, M, Tomaru, T, Lefterova, MI, Schug, J, Manduchi, E, Stoeckert CJ, Jr, Lazar, MA

Genes Dev 2010
8970730 Peroxisome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiology

Lemberger, T, Desvergne, B, Wahli, W

Annu Rev Cell Dev Biol 1996
11027271 Discrete roles for peroxisome proliferator-activated receptor gamma and retinoid X receptor in recruiting nuclear receptor coactivators

Yang, W, Rachez, C, Freedman, LP

Mol Cell Biol 2000
18039840 Alternative mechanisms by which mediator subunit MED1/TRAP220 regulates peroxisome proliferator-activated receptor gamma-stimulated adipogenesis and target gene expression

Ge, K, Cho, YW, Guo, H, Hong, TB, Guermah, M, Ito, M, Yu, H, Kalkum, M, Roeder, RG

Mol Cell Biol 2008
17011499 Transcriptional control of adipocyte formation

Farmer, SR

Cell Metab 2006
12037571 Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis

Ge, K, Guermah, M, Yuan, CX, Ito, M, Wallberg, AE, Spiegelman, BM, Roeder, RG

Nature 2002
12077340 Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription

Tan, NS, Shaw, NS, Vinckenbosch, N, Liu, P, Yasmin, R, Desvergne, B, Wahli, W, Noy, N

Mol Cell Biol 2002
14636573 Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha

Wallberg, AE, Yamamura, S, Malik, S, Spiegelman, BM, Roeder, RG

Mol Cell 2003
20194623 MED14 tethers Mediator to the N-terminal domain of PPAR{gamma} and is required for full transcriptional activity and adipogenesis

Grøntved, L, Madsen, MS, Boergesen, M, Roeder, RG, Mandrup, S

Mol Cell Biol 2010
19282365 The PPARgamma2 A/B-domain plays a gene-specific role in transactivation and cofactor recruitment

Bugge, A, Grøntved, L, Aagaard, MM, Borup, R, Mandrup, S

Mol Endocrinol 2009
10425206 PPARgamma activation induces the expression of the adipocyte fatty acid binding protein gene in human monocytes

Pelton, PD, Zhou, L, Demarest, KT, Burris, TP

Biochem Biophys Res Commun 1999
16407282 Down-regulation of histone deacetylases stimulates adipocyte differentiation

Yoo, EJ, Chung, JJ, Choe, SS, Kim, KH, Kim, JB

J Biol Chem 2006
7838715 Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alpha

Tontonoz, P, Graves, RA, Budavari, AI, Erdjument-Bromage, H, Lui, M, Hu, E, Tempst, P, Spiegelman, BM

Nucleic Acids Res 1994
Participants
Input
Output
Orthologous Events
PPARG:RXRA heterodimer binds to fatty acid-like ligands (Homo sapiens)
Authored
May, B  (2009-05-15)
Reviewed
Sethi, JK  (2011-02-10)
Created
May, B  (2010-03-23)
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