IκBβ interacts with the retinoid X receptor and inhibits retinoid- dependent transactivation in lipopolysaccharide-treated cells

Abstract

To elucidate the molecular action of the NFκB inhibitor IκBβ, we isolated a number of IκBβ interactors using the yeast two-hybrid system. These include the retinoid X receptor (RXR), whose interaction with IκBβ is significantly stimulated by the RXR ligand 9-cis-retinoic acid, as shown in the yeast system as well as the glutathione S-transferase pull down assays. RXR is a nuclear protein, whereas IκBβ accumulates in the nucleus only in cells stimulated with lipopolysaccharide or other inducers that result in prolonged activation of NFκB. Consistent with this, cotransfection with IκBβ specifically repressed the 9-cis-RA-induced transcriptional activities of RXR in an lipopolysaccharide-dependent manner. These results suggest a novel IκBβ-mediated antagonism between the signaling pathways of NFκB and RXR.