Juvenile hormones antagonize ecdysone actions through co-repressor recruitment to EcR/USP heterodimers
Juvenile hormones antagonize ecdysone actions through co-repressor recruitment to EcR/USP heterodimers
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DOI：
10.1016/j.bbrc.2004.05.156
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发表时间：
2004-07-16
影响因子：
3.1
通讯作者：
Kato, S
中科院分区：
文献类型：
--
作者：
Maki, A;Sawatsubashi, S;Kato, S
昆虫的发育是由蜕皮激素和保幼激素共同作用控制的。蜕皮激素的转录调控是通过两个核受体超家族成员--蜕皮激素受体(ECR)及其异源二聚体超二聚体(USP)介导的。虽然蜕皮激素20-羟基蜕皮酮作为ECR配体，通过ECR/USP异源二聚体激活转录，但保幼激素如保幼激素III(JH III)和甲氧基戊二酸(MA)通过USP的活性尚不清楚。在这里，我们证明了保幼激素作为USP配体，对依赖蜕皮激素的ECR反式激活具有抑制作用。JH III和MA结合的USP通过移位USP配体结合域α-螺旋12而显著抑制蜕皮激素依赖的ECR反式激活，而不影响ECR/USP异构化或DNA结合。此外，USP配体的转录抑制可被组蛋白去乙酰化抑制剂减弱。我们的结果表明，保幼激素作为USP配体，通过组蛋白脱乙酰酶复合体的募集来拮抗ECR介导的蜕皮激素作用。(C)2004 Elsevier Inc.保留所有权利。
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. (C) 2004 Elsevier Inc. All rights reserved.