Corepressors of PPARalpha Activation of PPARA by Fatty Acid Ligands Authored: May, B, 2009-05-30 16:45:51 Edited: May, B, 2009-05-30 16:45:51 Edited: May, B, 2009-06-08 PPAR-alpha is activated by binding polyunsaturated fatty acids especially those having 18-22 carbon groups and 2-6 double bonds. These ligands bind the C-terminal region of PPAR-alpha and include linoleic acid, linolenic acids, arachidonic acid, and eicosapentaenoic acid. The fibrate drugs are also agonists of PPAR-alpha.<br>Binding of a ligand causes a conformational change in PPAR-alpha so that it recruits coactivators. By analogy with the closely related receptor PPAR-gamma, PPAR-alpha probably binds TBL1 and TBLR1, which are responsible for recruiting the 19S proteasome to degrade corepressors during the exchange of corepressors for coactivators. The coactivators belong to the CBP-SRC-HAT complex (CBP/p300, SRC1, SRC2, SRC3, CARM1, SWI/SNF, BAF60C, PRIC320, and PRIC285), the ASC complex (PRIP/ASC2, PIMT), and the TRAP-DRIP-ARC-MEDIATOR complex (TRAP130, PBP/TRAP220). The coactivators contain LXXLL motifs (Nuclear Receptor Boxes) that interact with the AF-2 region in nuclear receptors such as PPAR-alpha. Pubmed10529898 Pubmed11226238 Pubmed11330046 Pubmed14980219 Pubmed16476485 Pubmed16503871 Pubmed17007889 Pubmed17306620 Pubmed18288277 Pubmed19289416 Pubmed9171241 Reactome Database ID Release 43400143 Reactome, http://www.reactome.org ReactomeREACT_19175 Reviewed: Kersten, S, 2009-06-08 PPARA:RXRA Coactivator Complex Coactivators of PPARalpha FABP1:Ligands of PPARA PPARA:RXRA Repressor Complex