Functional ecdysone receptor is the product of EcR and Ultraspiracle genes

Nature. 1993 Dec 2;366(6454):476-9. doi: 10.1038/366476a0.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Chromosomes / metabolism*
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila / genetics*
  • Drosophila Proteins
  • Ecdysone / metabolism*
  • Ecdysterone / analogs & derivatives
  • Ecdysterone / metabolism
  • Ecdysterone / pharmacology
  • Genes, Insect*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Retinoic Acid*
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism*
  • Retinoid X Receptors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Receptors, Steroid
  • Retinoid X Receptors
  • Transcription Factors
  • USP protein, Drosophila
  • ecdysone receptor
  • 26-iodoponasterone A
  • Ecdysone
  • muristerone A
  • Ecdysterone
  • DNA