DROSOPHILA HORMONE-RECEPTOR-38 - A 2ND PARTNER FOR DROSOPHILA USP SUGGESTS AN UNEXPECTED ROLE FOR NUCLEAR RECEPTORS OF THE NERVE GROWTH FACTOR-INDUCED PROTEIN B-TYPE

In Drosophila the response to the hormone ecdysone is mediated in part by Ultraspiracle (USP) and ecdysone receptor (EcR), which are members of the nuclear receptor superfamily. Heterodimers of these proteins b ind to ecdysone response elements (EcREs) and ecdysone to modulate tra nscription. Herein we describe Drosophila hormone receptor 38 (DHR38) and Bombyx hormone receptor 38 (BHR38), two insect homologues of rat n erve growth factor-induced protein B (NGFI-B). Although members of the NGFI-B family are thought to function exclusively as monomers, we sho w that DHR38 and BHR38 in fact interact strongly with USP and that thi s interaction is evolutionarily conserved, DHR38 can compete in vitro against EcR for dimerization with USP and consequently disrupt EcR-USP binding to an EcRE. Moreover, transfection experiments in Schneider c ells show that DHR38 can affect ecdysone-dependent transcription, This suggests that DHR38 plays a role in the ecdysone response and that mo re generally NGFI-B type receptors may be able to function as heterodi mers with retinoid X receptor type receptors in regulating transcripti on.