Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1993-01-12
2002-01-01
Scheiner, Toni R. (Department: 1642)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S007210, C435S007230, C436S064000, C436S501000, C436S503000, C436S813000
Reexamination Certificate
active
06335159
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to cell biology and more specifically to a novel receptor for retinoic acid.
Processes as diverse as growth, vision, and reproduction are dependent upon the presence of Vitamin A and its metabolites, which are termed retinoids. The molecular mechanisms which govern these diverse actions have remained unclear, however. Recently, the understanding of retinoid action has been advanced through the isolation of a specific nuclear receptor for retinoic acid, one of the physiologically active Vitamin A derivatives. See Petkovich et al., Nature 330:444-450 (1987); Giguere et al., Nature 330:624-629 (1987). This nuclear receptor, which is herein referred to as “RAR&agr;” and was previously referred to as “hRAR”, is a member of the steroid-thyroid hormone receptor family.
Receptors of the steroid-thyroid hormone family are intracellular proteins which consist of discrete DNA-binding regions and ligand-binding regions. The DNA-binding domain of steroid hormone receptors and related proteins consists of a cystein-rich region that has been highly conserved and that has the potential to form two zinc-binding fingers. The ligand binding region is specific to the cognate ligand.
Retinoids are known to be essential for the normal function of many epithelial tissues. However, the reported tissue-specific expression of RAR&agr; is uncharacteristic for a molecule expected to be a major mediator of retinoid action in epithelial tissues. Because of their critical role in mediating metabolism and growth, it is important to determine other receptors mediating retinoid action. Knowledge of retinoid receptors permits the manipulation and control of metabolic effects resulting from retinoid action.
There thus exists a need for the identification and characterization of receptors mediating the retinoid response and methods of manipulating and detecting these receptors. The present invention satisfies this need and provides related advantages as well.
SUMMARY OF THE INVENTION
This invention relates to substantially purified Retinoic Acid Receptor &egr; (RAR&egr;), having the amino acid sequence given in
FIG. 1
, and to the isolated nucleic acid encoding RAR&egr;. In addition, polypeptides comprising, and nucleic acids encoding, the DNA-binding and hormone-binding domain of the receptor are provided. Further, methods of detecting RAR&egr; and nucleic acids encoding RAR&egr; and its domains are provided.
REFERENCES:
patent: 5223606 (1993-06-01), Blaudin de Thé
patent: 5468617 (1995-11-01), De The et al.
patent: 321362 (1989-06-01), None
de Thé, et al.,Nature, vol. 330, No. 17, pp. 667-670, Dec. 1987.*
Brand, et al., “Identification of a Second Human Retinoic Acid Receptor”,Nature, 332:850-853 (1988).
Petkovich, et al., “A Human Retinoic Acid Receptor Which Belongs to the Family of Nuclear Receptors”,Nature, 330:444-450 (1987).
Giguere, et al., “Identification of a Receptor for the Morphogen Retinoic Acid”,Nature, 330:624-629 (1987).
Evans, “The Steroid and Thyroid Hormone Receptor Superfamily”,Science, 240:889-895 Figs. 2-5 (1988).
Umesono, “Retonoic Acid and Thyroid Hormone Induce Gene Expression Through a Common Responsive Element”,Nature, 336:262-265 Figs. 2-4 (1988).
Benbrook, “A New Retinoic Acid Receptor Identified From a Hepatocellular Carcinoma”,Nature, 333:669-672 Figs. 1-5 (1988).
Tizard, “Immunology, An Introduction”,Saunders Publ., 2 Ed:218-221 (1988).
Hudson, et al., “Practical Immunology”,Blackwell Sci. Publ., Alden Press, Oxford, p. 14 (1976).
Scheiner Toni R.
The Burnham Institute
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