Abstract
ALTHOUGH the biological activity of the insect moulting hormone ecdysone, is manifested through a hormonally regulated transcriptional cascade associated with chromosomal puffing1–3, a direct association of the receptor with the puff has yet to be established. The cloned ecdysone receptor4 (EcR) is by itself incapable of high-affinity DNA binding or transcriptional activation. Rather, these activities are dependent on heterodimer formation with Ultraspiracle5 (USP) the insect homologue of vertebrate retinoid X receptor6. Here we report that native EcR and USP are co-localized on ecdysone-responsive loci of polytene chromosomes. Moreover, we show that natural ecdysones selectively promote physical association between EcR and USP, and conversely, that high-affinity hormone binding requires both EcR and USP. Replacement of USP with retinoid X receptor produces heterodimers with distinct pharmacological and functional properties. These results redefine the ecdysone receptor as a dynamic complex whose activity may be altered by combinatorial interactions among subunits and ligand.
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References
Clever, U. & Karlson, P. Expl Cell Res. 20, 623–626 (1960).
Ashburner, M. in Developmental Studies on Giant Chromosomes (ed. Beermann, W.) 101–147 (Springer, New York, 1972).
Ashburner, M., Chihara, C., Meltzer, P. & Richards, G. Cold Spring Harbor Symp. quant. Biol. 38, 655–662 (1974).
Koelle, M. R. et al. Cell 67, 59–77 (1991).
Yao, T.-P., Segraves, W. A., Oro, A. E., McKeown, M. & Evans, R. M. Cell 71, 63–72 (1992).
Mangelsdorf, D. J. et al. Genes Dev. 6, 329–344 (1992).
Christianson, A. M. K. et al. Proc. natn. Acad. Sci. U.S.A. 89, 11503–11507 (1992).
Thomas, H. E., Stunnenberg, H. G. & Stewart, A. F. Nature 362, 471–475 (1993).
Riddihough, G. & Pelham, H. R. B. EMB0 J. 6, 3729–3734 (1987).
Christopherson, K. S., Mark, M. R., Bajaj, V. & Godowski, P. J. Proc. natn. Acad. Sci. U.S.A. 89, 6314–6318 (1992).
Allan, G. F. et al. J. biol. Chem. 267, 19513–19520 (1992).
Cherbas, P., Cherbas, L., Lee, S.-S. & Nakanishi, K. Proc. natn. Acad. Sci. U.S.A. 85, 2096–2100 (1988).
Koelle, M. R., Arbeitman, M. & Hogness, D. S. Proc. natn. Acad. Sci. U.S.A. (in the press).
Yang, N., Schüle, R., Mangelsdorf, D. M. & Evans, R. M. Proc. natn. Acad. Sci. U.S.A. 88, 3559–3563 (1991).
Forman, B. M., Casanova, J., Raaka, B. M., Ghysdael, J. & Samuels, H. H. Molec. Endocr. 6, 429–442 (1992).
Burtis, K. C., Thummel, C. S., Jones, C. W., Karim, F. D. & Hogness, D. S. Cell 61, 85–99 (1990).
Thummel, C. S., Burtis, K. C. & Hogness, D. S. Cell 61, 101–111 (1990).
Segraves, W. A. & Hogness, D. S. Genes Dev. 4, 204–219 (1990).
Talbot, W. S., Swyryd, E. A. & Hogness, D. S. Cell 73, 1323–1337 (1993).
Hollenberg, S. M. & Evans, R. M. Cell 55, 899–906 (1988).
Cherbas, L., Lee, K. & Cherbas, P. Genes Dev. 5, 120–131 (1991).
Zink, B., Engström, Y., Gehring, W. J. & Paro, R. EMBO J. 10, 153–172 (1991).
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Yao, TP., Forman, B., Jiang, Z. et al. Functional ecdysone receptor is the product of EcR and Ultraspiracle genes. Nature 366, 476–479 (1993). https://doi.org/10.1038/366476a0
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DOI: https://doi.org/10.1038/366476a0
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