Hormone response element compositions and assay

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

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435 697, 530330, 530350, C12Q 168, C12P 2102, C07K 706, C07K 14705

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active

055976930

ABSTRACT:
The present invention discloses steroid/thyroid hormone receptor DNA binding domain compositions that determine target gene specificity. The invention further discloses methods converting the target gene specificity of one receptor into the target gene specificity of another. Still further the invention discloses novel assays for identifying ligands for orphan hormone receptors. These assays are especially useful since they avoid the necessity of constructing chimeric genes and proteins in order to search for ligands that can activate a putative receptor.

REFERENCES:
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patent: 5171671 (1992-12-01), Evans et al.
patent: 5274077 (1993-12-01), Evans et al.
Green et al. Nature 325 (75-78) 1 Jan. 1987.
Green, et al., "The N-Terminal DNA-binding `Zinc Finger` of the Oestrogen and Glucocorticoid Receptors Determines Target Gene Specificity", EMBO J. 7, No. 10, 3037-3044 (1988).
Klock, et al., "Oestrogen and Glucocorticoid Responsive Elements Are Closely Related But Distinct", Nature 329, 734-736 (1987).
Freedman, et al., "The Function and Structure of the Metal Coordination Sites Within the Glucocorticoid Receptor DNA Binding Domain", Nature 334, 543-546 (1988).
Severne, et al., "Metal Binding `Finger` Structures in the Glucocorticoid Receptor Defined by Site-Directed Mutagenesis", EMBO J. 7, No. 8, 2503-2508 (1988).
Evans, R. M., "The Steroid and Thyroid Hormone Receptor Superfamily", Science 240, 889-895 (1988).
Mader, et al., "Three Amino Acids of the Oestrogen Receptor Are Essential to its Ability to Distinguish an Oestrogen From a Glucocorticoid Responsive Element", Nature 338, 271-274 (1989).
Thompson and Evans, "Trans-Activation by Thyroid Hormone Receptors: Functional Parallels With Steroid Hormone Receptors", Proc. Natl. Acad. Sci. USA 86, 3494-3498 (1989).
Umesono and Evans, "Determinants of Target Gene Specificity for Steroid/Thyroid Hormone Receptors", Cell 57, 1139-1146 (1989).
Hollenberg, S., and Evans, R., "Multiple and Cooperative Trans-Activation Domains of the Human Glucocorticoid Receptor", Cell vol. 55, 899-906 (Dec. 2, 1988).
Oro, A., Hollenberg, S., and Evans, R., "Transcriptional Inhibition by a Glucocorticoid Receptor-.beta.-Galactosidase Fusion Protein", Cell vol. 55, 1109-1114 (Dec. 23, 1988).
Kumar, V., Green, S., Stack, G., Berry, M., Jin, J., and Chambon, P., "Functional Domains of the Human Estrogen Receptor", Cell vol. 51, 941-951 (Dec. 24, 1987).
Giguere, V., Hollenber, S., Rosenfeld, M., and Evans, R., "Functional Domains of the Human Glucocorticoid Receptor", Cell vol. 46, 645-652 (Aug. 29, 1986).
Giguere, V., Ong, E., Segui, P., and Evans, R., "Identification of a Receptor for the Morphogen Retinoic Acid", Nature vol. 330, 624-629 (Dec. 1987).
Kumar, V., and Chambon, P., "The Estrogen Receptor Binds Tightly to Its Responsive Element as a Ligand-Induced Homodimer", Cell vol. 55, 145-156 (Oct. 7, 1988).
Hollenberg, S., Giguere, V., Segui, P., and Evans, R., "Colocalization of DNA-Binding and Transcriptional Activation Functions in the Human Glucocorticoid Receptor", Cell vol. 49, 39-46 (Apr. 10, 1987).

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