Pparg:Rxra heterodimer binds to fatty acids

Stable Identifier
Reaction [binding]
Mus musculus
SVG |   | 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
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J Biol Chem 2006
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Nucleic Acids Res 1994
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Biochem Biophys Res Commun 1999
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Mol Endocrinol 2009
20194623 MED14 tethers Mediator to the N-terminal domain of PPAR{gamma} and is required for full transcriptional activity and adipogenesis

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Mol Cell Biol 2010
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Mol Cell 2003
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Mol Cell Biol 2002
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Nature 2002
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Cell Metab 2006
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Mol Cell Biol 2008
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Mol Cell Biol 2000
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Annu Rev Cell Dev Biol 1996
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Genes Dev 2010
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Science 1999
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Tontonoz, P, Hu, E, Spiegelman, BM

Cell 1994
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