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  • Title: Cross-talk between orphan nuclear hormone receptor RZRalpha and peroxisome proliferator-activated receptor alpha in regulation of the peroxisomal hydratase-dehydrogenase gene.
    Author: Winrow CJ, Capone JP, Rachubinski RA.
    Journal: J Biol Chem; 1998 Nov 20; 273(47):31442-8. PubMed ID: 9813056.
    Abstract:
    The genes encoding the peroxisomal beta-oxidation enzymes enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (HD) and fatty acyl-CoA oxidase (AOx) are coordinately regulated by peroxisome proliferator-activated receptor alpha (PPARalpha)/9-cis-retinoic acid receptor (RXRalpha) heterodimers that transactivate these genes in a ligand-dependent manner via upstream peroxisome proliferator response elements (PPRE). Here we demonstrate that the monomeric orphan nuclear hormone receptor, RZRalpha, modulates PPARalpha/RXRalpha-dependent transactivation in a response-element dependent manner. Electrophoretic mobility shift analysis showed that RZRalpha bound specifically as a monomer to the HD-PPRE but not the AOx-PPRE. Determinants in the HD-PPRE for binding of RZRalpha were distinct from those required for interaction with PPARalpha/RXRalpha heterodimers. In transient transfections, RZRalpha stimulated ligand-mediated transactivation by PPARalpha from an HD-PPRE luciferase reporter in the absence of exogenously added RXRalpha, but did not affect PPARalpha-dependent transactivation of an AOx-PPRE reporter gene. These data illustrate cross-talk between the RZRalpha and PPARalpha signaling pathways at the level of the HD-PPRE in the regulation of the HD gene and characterize additional factors governing the regulation of peroxisomal beta-oxidation.
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