biostudies-literatureUnknown84Desmet SJUGentFWO<h4>Objective</h4>The peroxisome proliferator-activated receptor α (PPARα) is a transcription factor driving target genes involved in fatty acid β-oxidation. To what extent various PPARα interacting proteins may assist its function as a transcription factor is incompletely understood. An ORFeome-wide unbiased mammalian protein-protein interaction trap (MAPPIT) using PPARα as bait revealed a PPARα-ligand-dependent interaction with the orphan nuclear receptor estrogen-related receptor α (ERRα). The goal of this study was to characterize the nature of the interaction in depth and to explore whether it was of physiological relevance.<h4>Methods</h4>We used orthogonal protein-protein interaction assays and pharmacological inhibitors of ERRα in various systems to confirm a functional interactionMolecular metabolism101938https://www.ebi.ac.uk/biostudies/studies/S-EPMC11059514biostudies-literatureCrosstalk interactions between transcription factors ERRα and PPARα assist PPARα-mediated gene expression.PMC11059514Brunsveld LLibert CPeelman FRatman DTimmermans SDe Bosscher KDe Cauwer LLi YFijalkowska DStaels BDesmet SJVandenboorn EMFThommis JVan Hamme ETavernier JVanderhaeghen TClarisse DfalseCrosstalk interactions between transcription factors ERRα and PPARα assist PPARα-mediated gene expression.<h4>Objective</h4>The peroxisome proliferator-activated receptor α (PPARα) is a transcription factor driving target genes involved in fatty acid β-oxidation. To what extent various PPARα interacting proteins may assist its function as a transcription factor is incompletely understood. An ORFeome-wide unbiased mammalian protein-protein interaction trap (MAPPIT) using PPARα as bait revealed a PPARα-ligand-dependent interaction with the orphan nuclear receptor estrogen-related receptor α (ERRα). The goal of this study was to characterize the nature of the interaction in depth and to explore whether it was of physiological relevance.<h4>Methods</h4>We used orthogonal protein-protein interaction assays and pharmacological inhibitors of ERRα in various systems to confirm a functional interaction2024-01-01T00:00:00Z2024 Jun2026-06-02T22:47:18.838Z2026-04-21T03:13:29.595ZS-EPMC110595143863147810.1016/j.molmet.2024.101938