ROLE OF LIGAND IN RETINOID SIGNALING - 9-CIS-RETINOIC ACID MODULATES THE OLIGOMERIC STATE OF THE RETINOID-X-RECEPTOR

Many of the effects of retinoids on cells are mediated by the transcri ption factors known as retinoid nuclear receptors, but the mechanisms by which retinoids regulate the activity of the receptors are not know n. It was previously shown that the retinoid X receptor (RXR) forms te tramers with a high affinity. In the present work it is demonstrated t hat binding of 9-cis-retinoic acid to RXR leads to rapid dissociation of receptor tetramers. In addition, fluorescence anisotropy studies in dicate that ligand-binding results in a significant conformational cha nge such that holo-RXR is more compactly folded as compared to the ape -protein. These findings suggest that the initial event in signaling b y 9-cis-retinoic acid is a change in the oligomeric state of RXR. The data also imply that tetramer formation is a regulatory feature of the pathway by which RXR mediates the effects of retinoids on gene transc ription.