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Gene Review

EcR  -  Ecdysone receptor

Drosophila melanogaster

Synonyms: 20-hydroxy-ecdysone receptor, 20E receptor, CG1765, CG8347, DEcR, ...
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Disease relevance of EcR


High impact information on EcR


Biological context of EcR

  • We have identified the regions of Drosophila EcR and USP responsible for transcriptional activation of a semisynthetic Eip71CD promoter in Kc cells [9].
  • EcR helix 12 mutants (F645A and W650A) exhibit a dominant negative phenotype [9].
  • Mutagenesis reveals that AF2 function depends on EcR helix 12, but not on the cognate USP region [9].
  • A mutation, K497E, in the shared ligand-binding domain of the EcR isoforms caused elevated EcRB2-specific affinity for a canonical ecdysone response element [10].
  • Given the modest level of 20E-dependent activation, it is likely that the EcR-USP receptor acts synergistically with other transcription factors to bring about the high level of Vg gene expression [11].

Anatomical context of EcR

  • VgEcRE binds directly to EcR-USP produced in vitro and extracted from the vitellogenic fat body nuclei [11].
  • Cell-autonomous requirement of the USP/EcR-B ecdysone receptor for mushroom body neuronal remodeling in Drosophila [12].
  • Ligand-dependent de-repression via EcR/USP acts as a gate to coordinate the differentiation of sensory neurons in the Drosophila wing [13].
  • Moreover, a highly synergistically formed heterodimeric complex with the DNA-binding domain of EcR was observed on hsp27EcRE, but not on the native Usp response element from the chorion s15 gene promoter [14].
  • USP and EcR fusion proteins could be expressed in separate cell lines and then recombined following isolation to yield a ligand binding preparation with a dissociation constant (K(D)) for Ponasterone A of 1.5 nM and a total yield of 1.9 pmol ligand binding sites/mg protein [15].

Associations of EcR with chemical compounds

  • As with other retinoid X receptor heterodimers, EcR/USP affects gene transcription in a ligand-modulated manner [16].
  • Our observations suggest that silencing by the unliganded EcR/USP receptor and the subsequent release of silencing by moderate steroid levels may play an important role in coordinating early phases of steroid driven development [17].
  • Like, USP, it activates transcription in Drosophila Schneider S2 cells in a 20-hydroxyecdysone-dependent manner, via its interaction with the endogenous EcR protein [18].
  • EcRB1 is normally induced with a form of USP that is missing its DNA-binding domain (DBD), although potentiation by juvenile hormone (JH) III is reduced [10].
  • Whereas EcR-USP DNA-binding activity is unaffected by hormone, EcR-RXR DNA-binding activity is stimulated by either ecdysteroid or 9-cis-retinoic acid, demonstrating that hormone can play a role in heterodimer stabilization [19].

Physical interactions of EcR

  • These results are consistent with a model in which these latter processes are induced by a signal arising during the middle of the last larval stage but suppressed by the unliganded EcR/USP complex [17].
  • Polarity of the ecdysone receptor complex interaction with the palindromic response element from the hsp27 gene promoter [20].
  • The developmental profile of fully activated, ligand refractory receptor complexes closely correlated with that of yolk protein expression, suggesting an intimate involvement of the ecdysone receptor complex in both the induction and maintenance of high level expression of yolk protein genes [21].
  • Mutations in trr interact in eye development with EcR, and EcR and TRR can be co-immunoprecipitated on ecdysone treatment [22].
  • The 20E receptor can bind to each of the sequences recognized by DHR78 and DHR96, indicating that these proteins may compete with the receptor for binding to a common set of target sequences [23].

Regulatory relationships of EcR


Other interactions of EcR


Analytical, diagnostic and therapeutic context of EcR


  1. Expression of EcR and USP in Escherichia coli: purification and functional studies. Elke, C., Vögtli, M., Rauch, P., Spindler-Barth, M., Lezzi, M. Arch. Insect Biochem. Physiol. (1997) [Pubmed]
  2. Krüppel-like factor 4 (gut-enriched Krüppel-like factor) inhibits cell proliferation by blocking G1/S progression of the cell cycle. Chen, X., Johns, D.C., Geiman, D.E., Marban, E., Dang, D.T., Hamlin, G., Sun, R., Yang, V.W. J. Biol. Chem. (2001) [Pubmed]
  3. Null mutants of Drosophila B-type lamin Dm(0) show aberrant tissue differentiation rather than obvious nuclear shape distortion or specific defects during cell proliferation. Osouda, S., Nakamura, Y., de Saint Phalle, B., McConnell, M., Horigome, T., Sugiyama, S., Fisher, P.A., Furukawa, K. Dev. Biol. (2005) [Pubmed]
  4. Characterization of genes encoding members of the nuclear hormone receptor superfamily from Onchocerca volvulus. Yates, R.A., Tuan, R.S., Shepley, K.J., Unnasch, T.R. Mol. Biochem. Parasitol. (1995) [Pubmed]
  5. The Drosophila orphan nuclear receptor DHR38 mediates an atypical ecdysteroid signaling pathway. Baker, K.D., Shewchuk, L.M., Kozlova, T., Makishima, M., Hassell, A., Wisely, B., Caravella, J.A., Lambert, M.H., Reinking, J.L., Krause, H., Thummel, C.S., Willson, T.M., Mangelsdorf, D.J. Cell (2003) [Pubmed]
  6. TGF-beta signaling activates steroid hormone receptor expression during neuronal remodeling in the Drosophila brain. Zheng, X., Wang, J., Haerry, T.E., Wu, A.Y., Martin, J., O'Connor, M.B., Lee, C.H., Lee, T. Cell (2003) [Pubmed]
  7. Regulation of invasive cell behavior by taiman, a Drosophila protein related to AIB1, a steroid receptor coactivator amplified in breast cancer. Bai, J., Uehara, Y., Montell, D.J. Cell (2000) [Pubmed]
  8. Drosophila ecdysone receptor mutations reveal functional differences among receptor isoforms. Bender, M., Imam, F.B., Talbot, W.S., Ganetzky, B., Hogness, D.S. Cell (1997) [Pubmed]
  9. Transcription activation by the ecdysone receptor (EcR/USP): identification of activation functions. Hu, X., Cherbas, L., Cherbas, P. Mol. Endocrinol. (2003) [Pubmed]
  10. Analysis of transcriptional activity mediated by Drosophila melanogaster ecdysone receptor isoforms in a heterologous cell culture system. Beatty, J., Fauth, T., Callender, J.L., Spindler-Barth, M., Henrich, V.C. Insect Mol. Biol. (2006) [Pubmed]
  11. The vitellogenin gene of the mosquito Aedes aegypti is a direct target of ecdysteroid receptor. Martín, D., Wang, S.F., Raikhel, A.S. Mol. Cell. Endocrinol. (2001) [Pubmed]
  12. Cell-autonomous requirement of the USP/EcR-B ecdysone receptor for mushroom body neuronal remodeling in Drosophila. Lee, T., Marticke, S., Sung, C., Robinow, S., Luo, L. Neuron (2000) [Pubmed]
  13. Ligand-dependent de-repression via EcR/USP acts as a gate to coordinate the differentiation of sensory neurons in the Drosophila wing. Schubiger, M., Carré, C., Antoniewski, C., Truman, J.W. Development (2005) [Pubmed]
  14. Purification of Drosophila melanogaster ultraspiracle protein and analysis of its A/B region-dependent dimerization behavior in vitro. Rymarczyk, G., Grad, I., Rusek, A., Oświecimska-Rusin, K., Niedziela-Majka, A., Kochman, M., Ozyhar, A. Biol. Chem. (2003) [Pubmed]
  15. Expression and purification of the hormone binding domain of the Drosophila ecdysone and ultraspiracle receptors. Halling, B.P., Yuhas, D.A., Eldridge, R.R., Gilbey, S.N., Deutsch, V.A., Herron, J.D. Protein Expr. Purif. (1999) [Pubmed]
  16. The dual role of ultraspiracle, the Drosophila retinoid X receptor, in the ecdysone response. Ghbeish, N., Tsai, C.C., Schubiger, M., Zhou, J.Y., Evans, R.M., McKeown, M. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  17. The RXR ortholog USP suppresses early metamorphic processes in Drosophila in the absence of ecdysteroids. Schubiger, M., Truman, J.W. Development (2000) [Pubmed]
  18. An rxr/usp homolog from the parasitic nematode, Dirofilaria immitis. Shea, C., Hough, D., Xiao, J., Tzertzinis, G., Maina, C.V. Gene (2004) [Pubmed]
  19. Heterodimerization of the Drosophila ecdysone receptor with retinoid X receptor and ultraspiracle. Thomas, H.E., Stunnenberg, H.G., Stewart, A.F. Nature (1993) [Pubmed]
  20. Polarity of the ecdysone receptor complex interaction with the palindromic response element from the hsp27 gene promoter. Niedziela-Majka, A., Kochman, M., Ozyhar, A. Eur. J. Biochem. (2000) [Pubmed]
  21. Two distinct subpopulations of ecdysone receptor complex in the female mosquito during vitellogenesis. Miura, K., Wang, S.F., Raikhel, A.S. Mol. Cell. Endocrinol. (1999) [Pubmed]
  22. Methylation at lysine 4 of histone H3 in ecdysone-dependent development of Drosophila. Sedkov, Y., Cho, E., Petruk, S., Cherbas, L., Smith, S.T., Jones, R.S., Cherbas, P., Canaani, E., Jaynes, J.B., Mazo, A. Nature (2003) [Pubmed]
  23. Isolation, regulation, and DNA-binding properties of three Drosophila nuclear hormone receptor superfamily members. Fisk, G.J., Thummel, C.S. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  24. Temporal regulation of Drosophila salivary gland degeneration by the Broad-Complex transcription factors. Kuchárová-Mahmood, S., Raska, I., Mechler, B.M., Farkas, R. J. Struct. Biol. (2002) [Pubmed]
  25. A steroid-triggered transcriptional hierarchy controls salivary gland cell death during Drosophila metamorphosis. Jiang, C., Lamblin, A.F., Steller, H., Thummel, C.S. Mol. Cell (2000) [Pubmed]
  26. Broad-complex, but not ecdysone receptor, is required for progression of the morphogenetic furrow in the Drosophila eye. Brennan, C.A., Li, T.R., Bender, M., Hsiung, F., Moses, K. Development (2001) [Pubmed]
  27. Bombyx EcR (BmEcR) and Bombyx USP (BmCF1) combine to form a functional ecdysone receptor. Swevers, L., Cherbas, L., Cherbas, P., Iatrou, K. Insect Biochem. Mol. Biol. (1996) [Pubmed]
  28. Molecular determinants of differential ligand sensitivities of insect ecdysteroid receptors. Wang, S.F., Ayer, S., Segraves, W.A., Williams, D.R., Raikhel, A.S. Mol. Cell. Biol. (2000) [Pubmed]
  29. Transcript titers of ecdysteroid receptor components vary between tissues and stages during Drosophila development. Kim, S.J., Park, J.G., Lee, C.C. Mol. Cells (1999) [Pubmed]
  30. Characterization of the ligand-binding domain of the ecdysteroid receptor from Drosophila melanogaster. Grebe, M., Przibilla, S., Henrich, V.C., Spindler-Barth, M. Biol. Chem. (2003) [Pubmed]
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