ECDN protein and DNA encoding the same

Details ECDN protein and DNA encoding the same ECDN protein and DNA encoding the same

1996-05-02

1999-02-16

Elliott, George C.

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving nucleic acid

4351721, 536 231, 536 235, 536 243, 536 2431, 536 2433, C12Q 168, C07H 2102, C07H 2104

Patent

active

058719164

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

1. Field of the Invention
The present invention relates to an ECDN protein, which is a novel steroid hormone receptor-like protein, a DNA encoding the same and processes for the production and use of this protein.
2. Description of the Related Art
As steroid hormone receptor-like proteins, there have been found and identified a group of proteins which are homologous with each other in amino acid sequence. These proteins are respondent not only to steroid hormones but also to thyroid hormones and derivatives of fat-soluble vitamins such as vitamin D metabolites and natural and synthetic derivatives thereof, retinoic acid and natural and synthetic derivatives thereof and vitamin A metabolites. These ligand-dependent transcription regulating proteins constitute a superfamily and can regulate the expression of a specific gene by binding directly to a response element of a DNA specific for stimulation by a hormone or a ligand. It has been revealed that these receptor proteins play very important roles in the development, differentiation and the maintenance of homeostasis as transcription regulating factors which regulate the expression of specific Science, 240, 889 (1988)!. Thus, natural and synthetic derivatives which are capable of binding to these receptor proteins and-acting as ligands have been widely studied and applied in the fields of medicine, pharmacology and agriculture.
A group of proteins seemingly belonging to the superfamily of steroid hormone receptor proteins involve a group of a number of proteins which have been produced by molecular clonings effected by hybridizations under the lowered stringency, paying attention to the homology of DNA binding domains common to the superfamily. The group of these proteins include a group of proteins called orphan receptors, the ligands specific for which (1992)!. It is considered that studies on the identification of the ligands specific for these orphan receptors and functions of these orphan receptors as transcription regulating factors are highly important, since novel medical and biological findings applicable to medicines and agriculture might be provided thereby. For example, it has been clarified that the ligand of retinoid X receptor (RXR), which was once regarded as an orphan receptor, is 9-cis-retinoic acid and that RXR is a receptor al., NATURE, 359 (1992)!. It seems that in the proteins participating in the human transcriptional regulation mechanism depending on ligands, a number of receptors still remain unidentified. Therefore, it is highly meaningful to isolate and identify these receptors from the viewpoint of the application thereof to medicine and pharmacology too.


DISCLOSURE OF THE INVENTION



SUMMARY OF THE INVENTION

It is an object of the present invention to provide a novel receptor protein originating from human beings which belongs to the steroid/thyroid hormone receptor superfamily, a gene encoding the protein, a process for analyzing the function of a receptor with the use of the protein and a process for searching a ligand with the use of the protein, thus broadening the application field thereof.
As the results of comparison of the structures of proteins in a group constituting the superfamily of steroid hormone receptor-like proteins and analyses of the functions with the use of mutated receptors constructed via gene modification, it has been clarified that these proteins in the group comprise functional domains. It has been clarified that a domain consisting of 66 to 68 amino acids and having 2 zinc fingers shows the highest homology among the proteins in the group belonging to the superfamily and binds to a DNA, while a domain consisting of about 250 amino acids on the C-terminal side participates in the ligand-dependency 5, 2243 (1991)!. These steroid hormone receptor-like proteins have been detected and identified not only in mammals but also in insects. As a representative example thereof, a receptor to ecdysone, which is a steroid hormone controlling the metamorphoses of insects, is known a

REFERENCES:
Sommer et al "Minimal homology requirements for PCR primers" Nucleic Acids Research vol. 17(16):6749, 1989.
Science, vol. 240 pp. 889-895, 1988.
Th EMBO Journal, vol. 11, No. 3, pp. 1003-1013, 1992.
Nature, vol. 355, pp. 359-361, 1992.
Faseb J., vol. 5, pp. 2243-2249, 1992.
Cell, vol. 67, pp. 59-77, 1991.
Gene, vol. 147, pp. 273-276, 1994.
Proc. Natl. Acad. Sci. USA, vol. 91, pp. 10809-10813, 1994.

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