Receptor transcription-repression activity compositions and meth

Chemistry: molecular biology and microbiology – Spore forming or isolating process

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4353201, 530350, C12N 516, C12N 1585, C07K 14705

Patent

active

055784836

ABSTRACT:
Disclosed is an analysis of domains of receptors of the steroid/thyroid hormone superfamily, and particularly of the glucocorticoid receptor, to identify requirements for the trans-acting transcriptional repression activities of the receptors. Based on the analysis, certain novel receptor analogs are provided, as are various novel DNAs, expression vectors, cells and transgenic animals as well as novel methods of using trans-acting transcription-repressing analogs of the receptors in various applications. These applications include gene therapy, screening of cells in culture or transgenic animals for compositions effective to treat various diseases due to inability to properly respond to hormones of the steroid or thyroid hormone group, and screening of cells in culture for ligands that are capable, upon binding to one of the receptors, to activate its trans-acting transcription activating and trans-acting transcription-repressing activities.

REFERENCES:
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patent: 4981784 (1991-01-01), Evans et al.
Lavin et al., The Thyroid Hormone Receptor Binds to Multiple Domains of the Rat Growth Hormone 5'-Flanking Sequence, The Journal of Biological Chemistry vol. 263:9418-9426 (1988).
Thompson and Evans, Trans-activation by thyroid hormone receptors: Functional parallels with steroid hormone receptors, Proc. Natl. Acad. Sci. USA vol. 86:3493-3498 (1989).
Damm et al, Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist, Nature vol. 339:593-597 (1989).
Evans 1988 Science vol. 240:889-895.
Hollenberg et al 1987 Cell. 49:39-46.
Giguere et al. 1987 Nature 330:624.
Picard & Yamamoto 1987 EMBO J. 6(11): 3333-3340.

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