PPARG:RXRA:Corepressor Complex FABP4:Ligands of PPARG PPARG:RXRA Heterodimer Binds to Fatty Acid-like Ligands Authored: May, B, 2009-05-15 01:16:49 Edited: May, B, 2009-05-15 01:16:49 Edited: May, B, Gopinathrao, G, 2008-11-19 19:22:37 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).<br>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).<br>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).<br>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). Pubmed10075656 Pubmed17011499 Pubmed8706692 Pubmed8970730 Pubmed9065481 Reactome Database ID Release 43381309 Reactome, http://www.reactome.org ReactomeREACT_27257 Reviewed: D'Eustachio, P, 2009-05-26 22:09:50 Reviewed: Sethi, JK, 2011-02-09 Mediator Complex (consensus) PPARG:Fatty Acid:RXRA:Mediator:Coactivator Complex