Abstract
Peroxisome proliferators form a family of diverse xenobiotic compounds that includes hypolipidemic agents, herbicides, and plasticizers. These compounds activate transcription of a subset of nuclear genes including those encoding peroxisomal fatty acid beta-oxidation enzymes, whose elevated activities can lead to hepatocarcinogenesis. Induction of the genes encoding fatty acyl-CoA oxidase and hydratase-dehydrogenase, the first and second enzymes of the pathway, is mediated by peroxisome proliferator-activated nuclear receptors (PPARs) that bind to upstream responsive elements (PPREs) through heterodimerization with retinoid X receptors. We demonstrate that the chicken ovalbumin upstream promoter transcription factor 1 (COUP-TF1), another member of the nuclear hormone receptor superfamily, binds to the hydratase-dehydrogenase PPRE in vitro and in vivo and antagonizes PPAR-dependent signaling. These data suggest that members of the COUP-TF family play a role in modulating receptor-mediated activation of peroxisome proliferator-responsive genes.
Highlights
The administration of peroxisome proliferators leads to the coordinated transcriptional induction of the nuclear genes encoding the enzymes of the peroxisomal P-oxidation pathway: Factor (COUP-TF) Binds to a Peroxisome fatty acyl-CoA oxidase, enoyl-CoA hydratasd3-hydroxyacyl
Signal transduction by peroxisome proliferators is mediated by a similar mechanisminvolving ligandactivated receptorscalled peroxisome proliferator-activated receptors (PPARs) that belong to this family of transcription factors [18,19,20,21]
COUP-TFs bind as by peroxisome proliferator-activated nucleareceptors homodimers to diverse responseelementcsonsisting of (PPARs)thatbind to upstreamresponsive elements TGACCT repeats which exhibit wide variation in spacing and (PPREs) through heterodimerizatiownith retinoid X re- orientation [27]; they have the greatest affinity for ceptors.We demonstratethat the chickenovalbuminup- direct repeats separated by 1base pair (DR1)
Summary
The administration of peroxisome proliferators leads to the coordinated transcriptional induction of the nuclear genes encoding the enzymes of the peroxisomal P-oxidation pathway: Factor (COUP-TF) Binds to a Peroxisome fatty acyl-CoA oxidase, enoyl-CoA hydratasd3-hydroxyacyl-. Proliferator-responsive Element and Antagonizes Peroxisome (PPREs) havebeen identified in the 5”flanking regions of the genes encoding fatty acyl-CoA oxidase and HD [9,10,11,12] Both PPREs contain direct repeatsof the sequence TGACCT, which. PPARs bind cooperatively to PPREs through heterodimerization with the9-cis-retinoic acid receptor,R X R a Peroxisome proliferators form a family of diverxseenobiotciocmpounds that includes hypolipidemic agents, herbicides, and plasticizers. These compounds activate transcription of a subset of nuclear genes in-. The HD PPRE stream promoter transcription factor 1 (COUP-TaFnl)-, othemr ember of the nucleahrormonreeceptor superfamilyb,inds to the hydratase-dehydrogenase PPRE in vitro and in vivaond antagonizesPPAR-dependent signaling
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
