{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T17:25:12Z","timestamp":1782840312057,"version":"3.54.5"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"43","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,10,25]]},"abstract":"<jats:p>\n                    A number of insect effector genes activated by the steroid hormone 20-hydroxyecdysone (20E) are dually controlled by the ecdysteroid receptor (EcR\/USP) and products of ecdysteroid early responsive genes (\n                    <jats:italic>E74<\/jats:italic>\n                    ,\n                    <jats:italic>E75<\/jats:italic>\n                    , and\n                    <jats:italic>Broad<\/jats:italic>\n                    ). However, the molecular mechanism of this dual action is poorly understood. Here we examined transcriptional activation of the\n                    <jats:italic>vitellogenin<\/jats:italic>\n                    (\n                    <jats:italic>Vg<\/jats:italic>\n                    ) gene in the yellow fever mosquito,\n                    <jats:italic>Aedes aegypti<\/jats:italic>\n                    , by EcR\/USP and E74 in response to an elevation of 20E titers. There are two isoforms of the\n                    <jats:italic>Aedes E74<\/jats:italic>\n                    gene, AaE74A and AaE74B, which have a common C-terminal Ets DNA-binding domain and isoform-specific N termini in the female mosquito. Inhibiting expression of AaE74B but not AaE74A by RNA interference led to substantial reduction in the\n                    <jats:italic>Vg<\/jats:italic>\n                    gene expression. AaE74B and the ecdysteroid receptor synergistically enhanced 20E-induced transcription of the\n                    <jats:italic>Vg<\/jats:italic>\n                    promoter. This action required the E74-binding sites and the ecdysone response elements in the\n                    <jats:italic>Vg<\/jats:italic>\n                    5\u2032 regulatory region. Two-hybrid assays and coimmunoprecipitation analyses demonstrated direct interaction between AaE74B and AaEcR\/AaUSP. Moreover, disruption of this interaction by a dominant negative E74 mutant abolished the enhanced activation of\n                    <jats:italic>Vg<\/jats:italic>\n                    . Therefore, the cooperative interaction between AaE74B and the ecdysteroid receptor is required for high-level expression of the\n                    <jats:italic>Vg<\/jats:italic>\n                    gene\n                    <jats:italic>in vivo<\/jats:italic>\n                    . The synergistic activation is accomplished through their 20E-dependent protein-protein interaction on the gene promoter. This study reveals how the 20E direct-indirect regulation of an effector gene is achieved at the molecular level.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0503501102","type":"journal-article","created":{"date-parts":[[2005,10,17]],"date-time":"2005-10-17T20:34:14Z","timestamp":1129581254000},"page":"15506-15511","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":46,"title":["Synergistic action of E74B and ecdysteroid receptor in activating a 20-hydroxyecdysone effector gene"],"prefix":"10.1073","volume":"102","author":[{"given":"GuoQiang","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Entomology and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Entomology and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Entomology and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander S.","family":"Raikhel","sequence":"additional","affiliation":[{"name":"Department of Entomology and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,10,17]]},"reference":[{"key":"e_1_3_2_1_2","unstructured":"Riddiford L. 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