Peroxisome-proliferator-activated receptors (PPARs) α and γ are ligand-dependent transcription factors that are key regulators of lipid and carbohydrate homoeostasis. Fatty acids bind to the ligand-binding domains (LBDs) of PPARα and PPARγ and activate these receptors. To clarify whether fatty-acyl-CoAs interact directly with the LBDs of PPARα and PPARγ, we performed a competition binding assay with radiolabelled KRP-297, a known dual agonist for these receptors. We show here that fatty-acyl-CoAs bind directly to PPARα and PPARγ. Interestingly, fatty-acyl-CoAs, unlike fatty acids, failed to recruit steroid receptor co-activator 1 (SRC-1), on the basis of conformational changes in the LBDs of PPARα and PPARγ. Moreover, fatty-acyl-CoAs also markedly inhibited agonist-induced recruitment of SRC-1. These findings demonstrate that fatty-acyl-CoAs have a novel function in the signalling pathways of PPARα and PPARγ.
Fatty-acyl-CoA thioesters inhibit recruitment of steroid receptor co-activator 1 to α and γ isoforms of peroxisome-proliferator-activated receptors by competing with agonists
- Views Icon Views
- Share Icon Share
Koji MURAKAMI, Tomohiro IDE, Tomoko NAKAZAWA, Takashi OKAZAKI, Toshiro MOCHIZUKI, Takashi KADOWAKI; Fatty-acyl-CoA thioesters inhibit recruitment of steroid receptor co-activator 1 to α and γ isoforms of peroxisome-proliferator-activated receptors by competing with agonists. Biochem J 15 January 2001; 353 (2): 231–238. doi: https://doi.org/10.1042/bj3530231
Download citation file: