Fatty acid binding proteins shape the cellular response to activation of the glucocorticoid receptor

Liu, Bonan; Chandrashekaran, Indu R.; Ilyichova, Olga; Valour, Damien; Melchiore, Fabien; Bourrier, Chantal; Giganti, Adeline; Stephan, Jean-Philippe; Dacquet, Catherine; Genissel, Patrick; Gosgnach, Willy; Weaver, Richard J.; Porter, Christopher J.H.; Scanlon, Martin J.; Halls, Michelle L.

Glucocorticoids are steroid hormones that are essential for life in mammals. Therapeutically, they are some of the most cost-effective drugs for the treatment of inflammatory diseases ranging from skin rashes to COVID-19, but their use is limited by adverse effects. Glucocorticoids exert their effects via the glucocorticoid receptor, a type I nuclear hormone receptor which modulates gene expression. The transcriptional activity of some related, but nuclear restricted, type II nuclear hormone receptors can be enhanced by a family of intracellular transport proteins, the fatty acid binding proteins (FABPs). We find that the transcriptional activity of the GR can be altered by a sub-set of FABP family members dependent on the GR-ligand. The ability of some FABPs to selectively promote or limit the transcriptional activity of the GR in a ligand-dependent manner could facilitate the discovery of drugs that narrow GR activity to only the desired subset of therapeutically relevant genes.