title: Juvenile hormones antagonize ecdysone actions through co-repressor recruitment to EcR/USP heterodimers.
abstract: Insect development is controlled by the combined actions of ecdysteroid and juvenile hormones. Transcriptional control by ecdysteroid hormones is mediated via two nuclear receptor superfamily members, ecdysone receptor (EcR) and its heterodimeric partner, ultraspiracle (USP). Although the ecdysteroid hormone 20-hydroxyecdysone acts as an EcR ligand and activates transcription through EcR/USP heterodimers, the activity of juvenile hormones, such as Juvenile hormone III (JH III), and methoprenic acid (MA) via USP remains unclear. Here, we demonstrate that juvenile hormones act as USP ligands and exhibit suppressive effects on ecdysone-dependent EcR transactivation. JH III- and MA-bound USP markedly repressed ecdysone-dependent EcR transactivation through shifting of the USP ligand-binding domain alpha-helix 12 without affecting EcR/USP heterodimerization or DNA binding. Moreover, transcriptional repression by USP ligands was attenuated by a histone deacetylation inhibitor. Our results suggested that juvenile hormones serve as USP ligands that antagonize EcR-mediated ecdysone actions through the recruitment of histone deacetylase complexes.
authors.affiliation: The Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Maki
authors.forename: Shun
authors.initials: S
authors.lastname: Sawatsubashi
authors.forename: Saya
authors.initials: S
authors.lastname: Ito
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shirode
authors.forename: Eriko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yamagata
authors.forename: Alexander
authors.initials: A
authors.lastname: Kouzmenko
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takeyama
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism*; D011485:Protein Binding; D011987:Receptors, Steroid / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D012717:Sesquiterpenes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D011987:Receptors, Steroid; D012097:Repressor Proteins; D012717:Sesquiterpenes; D014157:Transcription Factors; C066030:USP protein, Drosophila; C055469:ecdysone receptor; C036585:juvenile hormone III