NF-AT polypeptides and polynucleotides

Details NF-AT polypeptides and polynucleotides NF-AT polypeptides and polynucleotides

1993-09-20

1998-11-17

Wax, Robert A.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 231, 536 243, C07H 2104

Patent

active

058378405

ABSTRACT:
The invention provides novel polypeptides which are associated with the transcription complex NF-AT, polynucleotides encoding such polypeptides, antibodies which are reactive with such polypeptides, polynucleotide hybridization probes and PCR amplification probes for detecting polynucleotides which encode such polypeptides, transgenes which encode such polypeptides, homologous targeting constructs that encode such polypeptides and/or homologously integrate in or near endogenous genes encoding such polypeptides, nonhuman transgenic animals which comprise functionally disrupted endogenous genes that normally encode such polypeptides, and transgenic nonhuman animals which comprise transgenes encoding such polypeptides. The invention also provides methods for detecting T cells (including activated T cells) in a cellular sample, methods for treating hyperactive or hypoactive T cell conditions, methods for screening for immunomodulatory agents, methods for diagnostic staging of lymphocyte differentiation, methods for producing NF-AT proteins for use as research or diagnostic reagents, methods for producing antibodies reactive with the novel polypeptides, and methods for producing transgenic nonhuman animals.

REFERENCES:
Clipstone and Crabtree, "Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation," Nature, 357:695-697 (1992).
Emmel, et al., "Cyclosporin A Specifically Inhibits Function of Nuclear Proteins Involved in T Cell Activation," Science, 246:1617-1620 (1989).
Flanagan et al., "Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A," Nature, 352:803-807 (1991).
McCaffrey et al., "NF-AT.sub.p, a T Lymphocyte DNA-binding Protein That is a Target for Calcineurin and Immunosuppressive Drugs," J. Biol. Chem., 268(5):3747-3752 (1993).
McCaffrey et al., "Isolation of the Cyclosporin-Sensitive T Cell Transcription Factor NFATp," Science, 262:750-754 (1993).
Northrop et al., "Characterization of the Nuclear and Cytoplasmic Components of the Lymphoid-specific Nuclear Factor of Activated T Cells (NF-AT) Complex," J. Biol. Chem., 268(4):2917-2923 (1993).
Northrop, S.P. et al. Nature 369:497-502 (1994).

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