Ecdysone receptors: From the ashburner model to structural biology

Annual Review of Entomology

Volumn 58, Issue , 2013, Pages 251-271

  Hill, Ronald J ^a   Billas, Isabelle M L ^b   Bonneton, François ^c   Graham, Lloyd D ^a   Lawrence, Michael C ^d,e  

^a CSIRO   (Australia)

^b UNIVERSITÉ DE STRASBOURG   (France)

^c UNIVERSITÉ LYON 1   (France)

^d WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^e UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

20 hydroxyecdysone; E75; EcR; evolution; USP; X ray structure

Indexed keywords

DROSOPHILA PROTEIN; ECDYSONE RECEPTOR; ECDYSTERONE; INSECT PROTEIN; STEROID RECEPTOR;

ANIMAL; DROSOPHILA MELANOGASTER; GENE EXPRESSION REGULATION; GENETICS; INSECT; METABOLISM; REVIEW;

ANIMALS; DROSOPHILA MELANOGASTER; DROSOPHILA PROTEINS; ECDYSTERONE; GENE EXPRESSION REGULATION; INSECT PROTEINS; INSECTS; RECEPTORS, STEROID;

EID: 84867611179     PISSN: 00664170     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev-ento-120811-153610     Document Type: Review

References (127)

1. Aguinaldo AM, Turbeville JM, Linford LS, Rivera MC, Garey JR, et al. 1997. Evidence for a clade of nematodes, arthropods and other moulting animals. Nature 387:489-93
2. Ashburner M. 1967. Patterns of puffing activity in salivary gland chromosomes of Drosophila. 1. Autosomal puffing patterns in a laboratory stock of Drosophila melanogaster. Chromosoma 21:398-428
3. Ashburner M. 1969. Patterns of puffing activity in salivary gland chromosomes of Drosophila. 2. Xchromosome puffing patterns of D. melanogaster and D. simulans. Chromosoma 27:47-63
4. Ashburner M. 1972. N-ethylmaleimide inhibition of induction of gene activity by hormone ecdysone. FEBS Lett. 22:265-69
5. Ashburner M. 1972. Patterns of puffing activity in salivary-gland chromosomes of Drosophila. 6. Induction by ecdysone in salivary-glands of D. melanogaster cultured in-vitro. Chromosoma 38:255-81
6. Ashburner M. 1973. Sequential gene activation by ecdysone in polytene chromosomes of Drosophila melanogaster. 1. Dependence upon ecdysone concentration. Dev. Biol. 35:47-61
7. Ashburner M. 1974. Sequential gene activation by ecdysone in polytene chromosomes of Drosophila melanogaster. 2. Effects of inhibitors of protein synthesis. Dev. Biol. 39:141-57
8. Ashburner M. 1990. Puffs, genes, and hormones revisited. Cell 61:1-3
9. Ashburner M, Chihara C, Meltzer P, Richards G. 1974. Temporal control of puffing activity in polytene chromosomes. Cold Spring Harb. Symp. Quant. Biol. 38:655-62
10. Ashburner M, Richards G. 1976. Sequential gene activation by ecdysone in polytene chromosomes of Drosophila melanogaster. 3. Consequences of ecdysone withdrawal. Dev. Biol. 54:241-55
11. Baker KD, Shewchuk LM, Kozlova T, Makishima M, Hassell A, et al. 2003. The Drosophila orphan nuclear receptor DHR38 mediates an atypical ecdysteroid signaling pathway. Cell 113:731-42
12. Becker HJ. 1959. Die Puffs der Speicheldrusenchromosomen von Drosophila melanogaster. 1. Beobachtungen zumDerhlaten des Puffmusters im Normalstamm und bei Zwei Mutanten, giant und lethal-giantlarvae. Chromosoma 10:654-78
13. Becker HJ. 1962. Die Puffs der Speicheldrusenchromosomen von Drosophila melanogaster. 2. Die Auslosung der Puffbildung, ihre Spezifitat und ihre Beziehung zur Funktion der Ringdruse. Chromosoma 13:341-84
14. Beermann W. 1952. Chromomeren Konstanz und spezifische Modifikationen der Chromosomenstruktur in der Entwicklung und Organdifferenzierung von Chironomus tentans. Chromosoma 5:139-98
15. Beermann W. 1956. Nuclear differentiation and functional morphology of chromosomes. Cold Spring Harb. Symp. Quant. Biol. 21:217-32
16. Billas IML, Browning C, Lawrence MC, Graham LD, Moras D, Hill RJ. 2009. The structure and function of ecdysone receptors. In Ecdysone: Structures and Functions, ed. G Smagghe, pp. 335-60. Berlin: Springer
17. Billas IML, Iwema T, Garnier JM, Mitschler A, Rochel N, Moras D. 2003. Structural adaptability in the ligand-binding pocket of the ecdysone hormone receptor. Nature 426:91-96
18. Billas IML, Moulinier L, Rochel N, Moras D. 2001. Crystal structure of the ligand-binding domain of the ultraspiracle protein USP, the ortholog of retinoid X receptors in insects. J. Biol. Chem. 276:7465-74
19. Birru W, Fernley RT, Graham LD, Grusovin J, Hill RJ, et al. 2010. Synthesis, binding and bioactivity of γ-methylene γ-lactam ecdysone receptor ligands: advantages of QSAR models for flexible receptors. Bioorg. Med. Chem. 18:5647-60
20. Bonneton F, Chaumot A, Laudet V. 2008. Annotation of Tribolium nuclear receptors reveals an increase in evolutionary rate of a network controlling the ecdysone cascade. Insect Biochem. Mol. Biol. 38:416-29
21. Bonneton F, Zelus D, Iwema T, Robinson-Rechavi M, Laudet V. 2003. Rapid divergence of the ecdysone receptor inDiptera and Lepidoptera suggests coevolution between EcR and USP-RXR. Mol. Biol. Evol. 20:541-53
22. Browning C, Martin E, Loch C, Wurtz JM, Moras D, et al. 2007. Critical role of desolvation in the binding of 20-hydroxyecdysone to the ecdysone receptor. J. Biol. Chem. 282:32924-34
23. Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, et al. 1997. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389:753-58
24. Burtis KC, Thummel CS, Jones CW, Karim FD, Hogness DS. 1990. The Drosophila 74EF early puff contains E74, a complex ecdysone-inducible gene that encodes two ETS-related proteins. Cell 61:85-99
25. Caceres L, Necakov AS, Schwartz C, Kimber S, Roberts IJH, Krause HM. 2011. Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75. Genes Dev. 25:1476-85
26. Carmichael JA, Lawrence MC, Graham LD, Pilling PA, Epa VC, et al. 2005. The X-ray structure of a hemipteran ecdysone receptor ligand-binding domain: comparison with a lepidopteran ecdysone receptor ligand-binding domain and implications for insecticide design. J. Biol. Chem. 280:22258-69
27. Chandra V, Huang P, Hamuro Y, Raghuram S, Wang Y, et al. 2008. Structure of the intact PPAR-γ-RXR-αnuclear receptor complex on DNA. Nature 456:350-56
28. Chao AT, Guild GM. 1986. Molecular analysis of the ecdysterone-inducible 2B5 early puff in Drosophila melanogaster. EMBO J. 5:143-50
29. Clayton GM, Peak-Chew SY, Evans RM, Schwabe JW. 2001. The structure of the ultraspiracle ligandbinding domain reveals a nuclear receptor locked in an inactive conformation. Proc. Natl. Acad. Sci. USA 98:1549-54
30. Clever U. 1964. Actinomycin and puromycin: effects on sequential gene activation by ecdysone. Science 146:794-95
31. Clever U, Karlson P. 1960. Induktion von Puff-Veranderungen in den Speicheldrusenchromosomen von Chironomus-tentans Durch Ecdyson. Exp. Cell Res. 20:623-26
32. Costantino BF, Bricker DK, Alexandre K, Shen K, Merriam JR, et al. 2008. A novel ecdysone receptor mediates steroid-regulated developmental events during the mid-third instar of Drosophila. PLoS Genet. 4:e1000102
33. Cruz J, Mane-Padros D, Bell?s X, Martin D. 2006. Functions of the ecdysone receptor isoform-A in the hemimetabolous insect Blattella germanica revealed by systemic RNAi in vivo. Dev. Biol. 297:158-71
34. Davis MB, Carney GE, Robertson AE, Bender M. 2005. Phenotypic analysis of EcR-A mutants suggests that EcR isoforms have unique functions during Drosophila development. Dev. Biol. 282:385-96
35. Devarakonda S, Harp JM, Kim Y, Ozyhar A, Rastinejad F. 2003. Structure of the heterodimeric ecdysone receptor DNA-binding complex. EMBO J. 22:5827-40
36. Dhadialla TS, Carlson GR, Le DP. 1998. New insecticides with ecdysteroidal and juvenile hormone activity. Annu. Rev. Entomol. 43:545-69
37. Dinan L, Hormann RE, Fujimoto T. 1999. An extensive ecdysteroid COMFA. J. Comput. Aided Mol. Des. 13:185-207
38. Dziedzic-Letka A, Rymarczyk G, Kaplon TM, Gorecki A, Szamborska-Gbur A, et al. 2011. Intrinsic disorder of Drosophila melanogaster hormone receptor 38 N-terminal domain. Proteins 79:376-92
39. Elmogy M, Iwami M, Sakurai S. 2004. Presence of membrane ecdysone receptor in the anterior silk gland of the silkworm Bombyx mori. Eur. J. Biochem. 271:3171-79
40. Elmogy M, Iwami M, Sakurai S. 2007. Solubilization of the ecdysone binding protein from anterior silk gland cell membranes of the silkworm, Bombyx mori. Zool. Sci. 24:971-77
41. Evans RM. 1988. The steroid and thyroid-hormone receptor superfamily. Science 240:889-95
42. Ewer J. 2005. How the ecdysozoan changed its coat. PLoS Biol. 3:e349
43. Flaig R, Greschik H, Peluso-Iltis C, Moras D. 2005. Structural basis for the cell-specific activities of the NGFI-B and the Nurr1 ligand-binding domain. J. Biol. Chem. 280:19250-58
44. Frand AR, Russel S, Ruvkun G. 2005. Functional genomic analysis of C. elegans molting. PLoS Biol. 3:e312
45. Fujii-Taira I, Yamaguchi S, Iijima R, Natori S, Homma KJ. 2009. Suppression of the ecdysteroidtriggered growth arrest by a novel Drosophila membrane steroid binding protein. FEBS Lett. 583:655-60
46. Gissendanner CR, Crossgrove K, Kraus KA, Maina CV, Sluder AE. 2004. Expression and function of conserved nuclear receptor genes in Caenorhabditis elegans. Dev. Biol. 266:399-416
47. Graham LD, Johnson WM, Pawlak-Skrzecz A, Eaton RE, Bliese M, et al. 2007. Ligand binding by recombinant domains from insect ecdysone receptors. Insect Biochem. Mol. Biol. 37:611-26
48. Graham LD, Johnson WM, Tohidi-Esfahani D, Pawlak-Skrzecz A, Bliese M, et al. 2009. Ecdysone receptors of pest insects-molecular cloning, characterisation, and a ligand binding domain-based fluorescence polarization screen. In Ecdysone: Structures and Functions, ed. G Smagghe, pp. 447-74. Berlin: Springer
49. Graham LD, Kotze AC, Fernley RT, Hill RJ. 2010. An ortholog of the ecdysone receptor protein (EcR) from the parasitic nematode Haemonchus contortus. Mol. Biochem. Parasitol. 171:104-7
50. Guay PS, Guild GM. 1991. The ecdysone-induced puffing cascade in Drosophila salivary-glands: A Broad-Complex early gene regulates intermolt and late gene-transcription. Genetics 129:169-75
51. Heming BS, ed. 2003. Insect Development and Evolution. Ithaca, NY: Cornell Univ. Press. 444 pp.
52. Henrich VC. 2012. The ecdysteroid receptor. In Insect Endocrinology, ed. LI Gilbert, pp. 177-218. Amsterdam: Elsevier
53. Hill RJ, Graham LD, Turner KA, Howell L, Tohidi-Esfahani D, et al. 2012. Structure and function of ecdysone receptors: interactions with ecdysteroids and synthetic agonists. Adv. Insect Physiol. 43:299-531
54. Hill RJ, Segraves WA, Choi D, Underwood PA, Macavoy E. 1993. The reaction with polytene chromosomes of antibodies raised against Drosophila E75A protein. Insect Biochem. Mol. Biol. 23:99-104
55. Holmwood G, Schindler M. 2009. Protein structure based rational design of ecdysone agonists. Bioorg. Med. Chem. 17:4064-70
56. Hu X, Cherbas L, Cherbas P. 2003. Transcription activation by the ecdysone receptor (EcR/USP): identification of activation functions. Mol. Endocrinol. 17:716-31
57. Hult EF, Tobe SS, Chang BSW. 2011. Molecular evolution of ultraspiracle protein (USP/RXR) in insects. PLoS ONE 6:e23416
58. Iwema T, Billas IM, Beck Y, Bonneton F, Nierengarten H, et al. 2007. Structural and functional characterization of a novel type of ligand-independent RXR-USP receptor. EMBO J. 26:3770-82
59. Iwema T, Chaumot A, Studer RA, Robinson-Rechavi M, Billas IM, et al. 2009. Structural and evolutionary innovation of the heterodimerization interface between USP and the ecdysone receptor EcR in insects. Mol. Biol. Evol. 26:753-68
60. Jacob F, Monod J. 1961. Genetic regulatory mechanisms in synthesis of proteins. J. Mol. Biol. 3:318-56
61. Jensen EV, Desombre ER. 1972. Mechanism of action of female sex-hormones. Annu. Rev. Biochem. 41:203-30
62. Jensen EV, Hurst DJ, Desombre ER, Jungblut PW. 1967. Sulfhydryl groups and estradiol-receptor interaction. Science 158:385-87
63. Jindra M, Palli SR, Riddiford LM. 2013. The juvenile hormone signaling pathway in insect development. Annu. Rev. Entomol. 58:181-204
64. Karlson P. 1965. Biochemical studies of ecdysone control of chromosomal activity. J. Cell. Physiol. 66:69-75
65. King-Jones K, Thummel CS. 2005. Nuclear receptors-a perspective from Drosophila. Nat. Rev. Genet. 6:311-23
66. Koelle MR, Talbot WS, Segraves WA, Bender MT, Cherbas P, Hogness DS. 1991. The Drosophila EcR gene encodes an ecdysone receptor, a new member of the steroid-receptor superfamily. Cell 67:59-77
67. Kroeger H. 1963. Chemical nature of system controlling gene activities in insect cells. Nature 200:1234-35
68. Lafont R, Koolman J. 2009. Diversity of ecdysteroids in animal species. In Ecdysone: Structures and Functions, ed. G Smagghe, pp. 47-71. Berlin: Springer
69. Lezzi M, Bergman T, Henrich VC, Vogtli M, Fromel C, et al. 2002. Ligand-induced heterodimerization between the ligand binding domains of the Drosophila ecdysteroid receptor and ultraspiracle. Eur. J. Biochem. 269:3237-45
70. Li C, Schwabe JWR, Banayo E, Evans RM. 1997. Coexpression of nuclear receptor partners increases their solubility and biological activities. Proc. Natl. Acad. Sci. USA 94:2278-83
71. Magner DB, Antebi A. 2008. Caenorhabditis elegans nuclear receptors: insights into life traits. Trends Endocrinol. Metab. 19:153-60
72. Markov GV, Laudet V. 2011. Origin and evolution of the ligand-binding ability of nuclear receptors. Mol. Cell Endocrinol. 334:21-30
73. Maroy P, Dennis R, Beckers C, Sage BA, O'Connor JD. 1978. Demonstration of an ecdysteroid receptor in a cultured cell line of Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 75:6035-38
74. Marvin KA, Reinking JL, Lee AJ, Pardee K, Krause HM, Burstyn JN. 2009. Nuclear receptors Homo sapiens Rev-erbβ and Drosophila melanogaster E75 are thiolate-ligated heme proteins which undergo redox-mediated ligand switching and bind CO and NO. Biochemistry 48:7056-71
75. Minakuchi C, Ogura T, Miyagawa H, Nakagawa Y. 2007. Effects of the structures of ecdysone receptor (EcR) and ultraspiracle (USP) on the ligand-binding activity of the EcR/USP heterodimer. J. Pestic. Sci. 32:379-84
76. Monod J, Jacob F. 1961. General conclusions: teleonomic mechanisms in cellular metabolism, growth, and differentiation. Cold Spring Harb. Symp. Quant. Biol. 26:389-401
77. Mouillet JF, Henrich VC, Lezzi M, Vogtli M. 2001. Differential control of gene activity by isoforms A, B1 and B2 of the Drosophila ecdysone receptor. Eur. J. Biochem. 268:1811-19
78. Nakagawa Y, Henrich VC. 2009. Arthropod nuclear receptors and their role in molting. FEBS J. 276:6128-57
79. Nakagawa Y, Sakai A, Magata F, Ogura T, Miyashita M, Miyagawa H. 2007. Molecular cloning of the ecdysone receptor and the retinoid X receptor from the scorpion Liocheles australasiae. FEBS J. 274:6191-203
80. Nocula-Lugowska M, Rymarczyk G, Lisowski M, Ozyhar A. 2009. Isoform-specific variation in the intrinsic disorder of the ecdysteroid receptor N-terminal domain. Proteins 76:291-308
81. Nowickyj SM, Chithalen JV, Cameron D, Tyshenko MG, Petkovich M, et al. 2008. Locust retinoid X receptors: 9-cis-retinoic acid in embryos from a primitive insect. Proc. Natl. Acad. Sci. USA 105:9540-45
82. Ogura T, Minakuchi C, Nakagawa Y, Smagghe G, Miyagawa H. 2005. Molecular cloning, expression analysis and functional confirmation of ecdysone receptor and ultraspiracle from the Colorado potato beetle Leptinotarsa decemlineata. FEBS J. 272:4114-28
83. Pardee KI, Xu XH, Reinking J, Schuetz A, Dong AP, et al. 2009. The structural basis of gas-responsive transcription by the human nuclear hormone receptor REV-ERBβ. PLoS Biol. 7:384-98
84. Parihar M, Minton RL, Flowers S, Holloway A, Morehead BE, et al. 2010. The genome of the nematode Pristionchus pacificus encodes putative homologs of RXR/USP and Ec R. Gen. Comp. Endocrinol. 167:11-17
85. Pelling C. 1964. Ribonukleinsaure-synthese der Riesenchromosomen. Autoradiographische Untersuchungen an Chironomus tentans. Chromosoma 15:71-122
86. Rees HH. 1989. Zooecdysteroids: structures and occurrence. In Ecdysone: From Chemistry to Mode of Action, ed. J Koolman, pp. 28-38. Stuttgart, Ger. : Georg Thieme
87. Reinking J, Lam MMS, Pardee K, Sampson HM, Liu SY, et al. 2005. The Drosophila nuclear receptor E75 contains heme and is gas responsive. Cell 122:195-207
88. Renaud JP, Moras D. 2000. Structural studies on nuclear receptors. Cell Mol. Life Sci. 57:1748-69
89. Richards G. 1978. Sequential gene activation by ecdysone in polytene chromosomes of Drosophila melanogaster. 4. Inhibition by juvenile hormones. Dev. Biol. 66:32-42
90. Riddiford LM, Cherbas P, Truman JW. 2000. Ecdysone receptors and their biological actions. Vitam. Horm. 60:1-73
91. Riddiford LM, Hiruma K, Zhou X, Nelson CA. 2003. Insights into the molecular basis of the hormonal control of molting and metamorphosis from Manduca sexta and Drosophila melanogaster. Insect Biochem. Mol. Biol. 33:1327-38
92. Rochette-Egly C. 2003. Nuclear receptors: integration of multiple signalling pathways through phosphorylation. Cell Signal. 15:355-66
93. Savard J, Tautz D, Richards S, Weinstock GM, Gibbs RA, et al. 2006. Phylogenomic analysis reveals bees and wasps (Hymenoptera) at the base of the radiation of holometabolous insects. Genome Res. 16: 1334-38
94. Segraves WA. 1987. Molecular and genetic analysis of the E75 ecdysone-responsive gene of Drosophila melanogaster. PhD thesis. Stanford Univ. Stanford, Calif. 299 pp.
95. Segraves WA, Hogness DS. 1990. The E75 ecdysone-inducible gene responsible for the 75B early puff in Drosophila encodes two new members of the steroid-receptor superfamily. Genes Dev. 4:204-19
96. Shea C, Hough D, Xiao J, Tzertzinis G, Maina CV. 2004. An RXR/USP homolog from the parasitic nematode, Dirofilaria immitis. Gene 324:171-82
97. Shea C, Richer J, Tzertzinis G, Maina CV. 2010. An EcR homolog from the filarial parasite, Dirofilaria immitis requires a ligand-activated partner for transactivation. Mol. Biochem. Parasitol. 171:55-63
98. Sieber MH, Thummel CS. 2012. Coordination of triacylglycerol and cholesterol homeostasis by DHR96 and the Drosophila LipA homolog magro. Cell Metab. 15:122-27
99. Sladek FM. 2011. What are nuclear receptor ligands? Mol. Cell Endocrinol. 334:3-13
100. Sluder AE, Maina CV. 2001. Nuclear receptors in nematodes: themes and variations. Trends Genet. 17:206-13
101. Spindler KD, Honl C, Tremmel C, Braun S, Ruff H, Spindler-Barth M. 2009. Ecdysteroid hormone action. Cell Mol. Life Sci. 66:3837-50
102. Srivastava DP, Yu EJ, Kennedy K, Chatwin H, Reale V, et al. 2005. Rapid, nongenomic responses to ecdysteroids and catecholamines mediated by a novel Drosophila G-protein-coupled receptor. J. Neurosci. 25:6145-55
103. Takahashi K, Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-76
104. Talbot WS, Swyryd EA, Hogness DS. 1993. Drosophila tissues with different metamorphic responses to ecdysone express different ecdysone receptor isoforms. Cell 73:1323-37
105. Tan A, Palli SR. 2008. Edysone receptor isoforms play distinct roles in controlling molting and metamorphosis in the red flour beetle, Tribolium castaneum. Mol. Cell. Endocrinol. 291:42-49
106. Telford MJ, Bourlat SJ, Economou A, Papillon D, Rota-Stabelli O. 2008. The evolution of theEcdysozoa. Philos. Trans. R. Soc. Lond. B Biol. Sci. 363:1529-37
107. Thomas HE, Stunnenberg HG, Stewart AF. 1993. Heterodimerization of the Drosophila ecdysone receptor with retinoid-X receptor and ultraspiracle. Nature 362:471-75
108. Thummel CS. 2002. Ecdysone-regulated puff genes 2000. Insect Biochem. Mol. Biol. 32:113-20
109. Thummel CS, Burtis KC, Hogness DS. 1990. Spatial and temporal patterns of E74 transcription during Drosophila development. Cell 61:101-11
110. Toft D, Shyamala G, Gorski J. 1967. A receptor molecule for estrogens: studies using a cell-free system. Proc. Natl. Acad. Sci. USA 57:1740-43
111. Tohidi-Esfahani D, Graham LD, Hannan GN, Simpson AM, Hill RJ. 2011. An ecdysone receptor from the pentatomomorphan, Nezara viridula, shows similar affinities for molting hormones makisterone A and 20-hydroxyecdysone. Insect Biochem. Mol. Biol. 41:77-89
112. Tohidi-Esfahani D, Lawrence MC, Graham LD, Hannan GN, Simpson AM, Hill RJ. 2011. Isoforms of the heteropteran Nezara viridula ecdysone receptor: protein characterisation, RH5992 insecticide binding and homology modelling. Pest Manag. Sci. 67:1457-67
113. Tomkins GM. 1974. Regulation of gene expression in mammalian cells. Harvey Lect. 68:37-65
114. Truman JW. 2005. Hormonal control of insect ecdysis: endocrine cascades for coordinating behavior with physiology. Vitam. Horm. 73:1-30
115. Tzertzinis G, Egana AL, Palli SR, Robinson-Rechavi M, Gissendanner CR, et al. 2010. Molecular evidence for a functional ecdysone signaling system in Brugia malayi. PLoS Negl. Trop. Dis. 4: e625
116. Urness LD, Thummel CS. 1990. Molecular interactions within the ecdysone regulatory hierarchy: DNA-binding properties of the Drosophila ecdysone-inducible E74A protein. Cell 63:47-61
117. Wang SF, Li C, Sun G, Zhu J, Raikhel AS. 2002. Differential expression and regulation by 20-hydroxyecdysone of mosquito ecdysteroid receptor isoforms A and B. Mol. Cell Endocrinol. 196:29-42
118. Wang Z, Benoit G, Liu J, Prasad S, Aarnisalo P, et al. 2003. Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors. Nature 423:555-60
119. Watanabe T, Takeuchi H, Kubo T. 2010. Structural diversity and evolution of the N-terminal isoformspecific region of ecdysone receptor-A and-B1 isoforms in insects. BMC Evol. Biol. 10:40
120. White KP, Hurban P, Watanabe T, Hogness DS. 1997. Coordination of Drosophila metamorphosis by two ecdysone-induced nuclear receptors. Science 276:114-17
121. Wing KD. 1988. RH-5849, a nonsteroidal ecdysone agonist: effects on a Drosophila cell-line. Science 241:467-69
122. Yao TP, Forman BM, Jiang ZY, Cherbas L, Chen JD, et al. 1993. Functional ecdysone receptor is the product of EcR and ultraspiracle genes. Nature 366:476-79
123. Yao TP, Segraves WA, Oro AE, McKeown M, Evans RM. 1992. Drosophila ultraspiracle modulates ecdysone receptor function via heterodimer formation. Cell 71:63-72
124. Yu JY, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, et al. 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917-20
125. Yund MA, King DS, Fristrom JW. 1978. Ecdysteroid receptors in imaginal disks of Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 75:6039-43
126. Zdobnov EM, Bork P. 2007. Quantification of insect genome divergence. Trends Genet. 23:16-20
127. Chaumot A, Da Lage J-L, Maestro O, Martin D, Iwema T, et al. 2012. Molecular adaptation and resilience of the insect's nuclear receptor USP. BMC Evol. Biol. In press