Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1990-08-06
1992-12-15
Lacey, David L.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
435 697, 4352573, 4353201, 530350, 536 27, C12N 1512, C12N 1562, C12N 1563, C07K 1300
Patent
active
051716712
ABSTRACT:
A novel retinoic acid receptor is disclosed. The novel receptor is encoded for by cDNA carried on plasmid phRAR1, which has been deposited with the American Type Culture Collection for patent purposes. Chimeric receptor proteins are also disclosed. The chimera are constructed by exchanging functional domains between the glucocorticoid, the mineralocorticoid, the estrogen-related, the thyroid and the retinoic acid receptors. In addition, a novel method for identifying functional ligands for receptor proteins is disclosed. The method, which takes advantage of the modular structure of the hormone receptors and the idea that the functional domains may be interchangeable, replaces the DNA-binding domain of a putative novel receptor with the DNA-binding domain of a known receptor such as the glucocorticoid receptor. The resulting chimeric construction, when expressed in cells, produces a hybrid receptor whose activation of a ligand-(e.g., glucocorticoid) inducible promoter is dependent on the presence of the new ligand. The novel method is illustrated in part by showing that the ligand for the new receptor protein is the retinoid, retinoic acid.
REFERENCES:
Nature 332:850-853, Apr. 28, 1988, Brard et al., Identification of a second human retinoic acid receptor.
Science 240:889-895, May 13, 1988, Evans, The Steroid and Thyroid Hormone Receptor Superfamily.
Nature 330:624-629, Dec. 17, 1987, Giguere et al., Identification of a receptor for the morphogen retinoic acid.
Nature 330:444-450, Dec. 17, 1987, Petkovich et al., A human retinoic acid receptor which belongs to the family of nuclear receptors.
Nature 330:420-421, Dec. 3, 1987, Robertson, Towards a biochemistry of morphogenesis.
Pharm. Rev. 36:935-1005, 1984, Chytil, Retinoic Acid: Biochemistry, Pharmacology, Toxicology, and Therapeutic Use.
PNAS, 84:5645-5649, Aug. 1987, Shubeita et al., Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid . . . .
Evans Ronald M.
Giguere Vincent
Ong Estelita S.
Segui Prudimar S.
Thompson Catherine C.
Lacey David L.
The Salk Institute for Biological Studies
Ulm John D.
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