title: Functional ecdysone receptor is the product of EcR and Ultraspiracle genes.
abstract: Although the biological activity of the insect moulting hormone ecdysone, is manifested through a hormonally regulated transcriptional cascade associated with chromosomal puffing, a direct association of the receptor with the puff has yet to be established. The cloned ecdysone receptor (EcR) is by itself incapable of high-affinity DNA binding or transcriptional activation. Rather, these activities are dependent on heterodimer formation with Ultraspiracle (USP) the insect homologue of vertebrate retinoid X receptor. Here we report that native EcR and USP are co-localized on ecdysone-responsive loci of polytene chromosomes. Moreover, we show that natural ecdysones selectively promote physical association between EcR and USP, and conversely, that high-affinity hormone binding requires both EcR and USP. Replacement of USP with retinoid X receptor produces heterodimers with distinct pharmacological and functional properties. These results redefine the ecdysone receptor as a dynamic complex whose activity may be altered by combinatorial interactions among subunits and ligand.
authors.affiliation: Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California 92037.
authors.forename: T P
authors.initials: TP
authors.lastname: Yao
authors.forename: B M
authors.initials: BM
authors.lastname: Forman
authors.forename: Z
authors.initials: Z
authors.lastname: Jiang
authors.forename: L
authors.initials: L
authors.lastname: Cherbas
authors.forename: J D
authors.initials: JD
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: McKeown
authors.forename: P
authors.initials: P
authors.lastname: Cherbas
authors.forename: R M
authors.initials: RM
authors.lastname: Evans
mesh_terms: D000818:Animals; D002460:Cell Line; D002875:Chromosomes / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D004440:Ecdysone / Q000378:metabolism*; D004441:Ecdysterone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017344:Genes, Insect; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D047488:Retinoid X Receptors; D014157:Transcription Factors; C066030:USP protein, Drosophila; C055469:ecdysone receptor; C055470:26-iodoponasterone A; D004440:Ecdysone; C055348:muristerone A; D004441:Ecdysterone; D004247:DNA