title: Drosophila hormone receptor 38: a second partner for Drosophila USP suggests an unexpected role for nuclear receptors of the nerve growth factor-induced protein B type.
abstract: 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 bind to ecdysone response elements (EcREs) and ecdysone to modulate transcription. Herein we describe Drosophila hormone receptor 38 (DHR38) and Bombyx hormone receptor 38 (BHR38), two insect homologues of rat nerve growth factor-induced protein B (NGFI-B). Although members of the NGFI-B family are thought to function exclusively as monomers, we show that DHR38 and BHR38 in fact interact strongly with USP and that this 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 cells show that DHR38 can affect ecdysone-dependent transcription. This suggests that DHR38 plays a role in the ecdysone response and that more generally NGFI-B type receptors may be able to function as heterodimers with retinoid X receptor type receptors in regulating transcription.
authors.affiliation: Department of Molecular and Cell Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Sutherland
authors.forename: T
authors.initials: T
authors.lastname: Kozlova
authors.forename: G
authors.initials: G
authors.lastname: Tzertzinis
authors.forename: F C
authors.initials: FC
authors.lastname: Kafatos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D012831:Bombyx / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000378:metabolism; D004440:Ecdysone / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D007301:Insect Hormones / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011494:Protein Kinases; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D018010:Receptors, Invertebrate Peptide / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C095176:Hr38 protein, Drosophila; D007301:Insect Hormones; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D018010:Receptors, Invertebrate Peptide; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C066030:USP protein, Drosophila; C055469:ecdysone receptor; D004440:Ecdysone; D011494:Protein Kinases; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors