I-KAPPA-B-BETA INTERACTS WITH THE RETINOID-X-RECEPTOR AND INHIBITS RETINOID-DEPENDENT TRANSACTIVATION IN LIPOPOLYSACCHARIDE-TREATED CELLS

To elucidate the molecular action of the NF kappa B inhibitor I kappa B beta, we isolated a number of I kappa B beta interactors using the y east two-hybrid system, These include the retinoid X receptor (RXR), w hose interaction with I kappa B beta is significantly stimulated by th e RXR ligand g-cis-retinoic acid, as shown in the yeast system as well as the glutathione S-transferase pull down assays. RXR is a nuclear p rotein, whereas I kappa B beta accumulates in the nucleus only in cell s stimulated with lipopolysaccharide or other inducers that result in prolonged activation of NF kappa beta. Consistent with this, cotransfe ction with I kappa B beta specifically repressed the 9-cis-RA-induced transcriptional activities of RXR in an lipopolysaccharide-dependent m anner. These results suggest a novel I kappa B beta-mediated antagonis m between the signaling pathways of NF kappa B and RXR.