FUNCTIONAL ECDYSONE RECEPTOR IS THE PRODUCT OF ECR AND ULTRASPIRACLE GENES

ALTHOUGH the biological activity of the insect moulting hormone ecdyso ne, is manifested through a hormonally regulated transcriptional casca de associated with chromosomal puffing1-3, a direct association of the receptor with the puff has yet to be established. The cloned ecdysone receptor4 (EcR) is by itself incapable of high-affinity DNA binding o r transcriptional activation. Rather, these activities are dependent o n heterodimer formation with Ultraspiracle5 (USP) the insect homologue of vertebrate retinoid X receptor6. Here we report that native EcR an d USP are co-localized on ecdysone-responsive loci of polytene chromos omes. Moreover, we show that natural ecdysones selectively promote phy sical association between EcR and USP, and conversely, that high-affin ity hormone binding requires both EcR and USP. Replacement of USP with retinoid X receptor produces heterodimers with distinct pharmacologic al and functional properties. These results redefine the ecdysone rece ptor as a dynamic complex whose activity may be altered by combinatori al interactions among subunits and ligand.