The invention relates generally to compositions of and methods for obtaining ubiquitous, nuclear receptor (UR) polypeptides. The invention also relates to polynucleotides encoding UR polypeptides, recombinant host cells and vectors containing UR-encoding polynucleotide sequences, and recombinant UR polypeptides. By way of example, the invention discloses the cloning and functional expression of at least two different UR polypeptides. The invention also includes methods for using the isolated, recombinant receptor polypeptides in assays designed to select substances which interact with UR polypeptides for use in diagnostic, drug design and therapeutic applications.
The present application is a continuation-in-part of U.S. Ser. No. 08/152,003, filed Nov. 10, 1993, abandoned, the entire text and figures of which disclosures are specifically incorporated herein by reference without disclaimer.
This invention provides an isolated receptor having the amino acid sequence of FIG. 1 (SEQ ID NO:2) or substantially the same amino acid sequence as the amino acid sequence shown in FIG. 1 (SEQ ID NO:2) or an amino acid sequence functionally similar to that sequence, and DNA sequences encoding such a receptor.
This invention provides an isolated receptor having the amino acid sequence of FIG. 1 (SEQ ID NO:2) or substantially the same amino acid sequence as the amino acid sequence shown in FIG. 1 (SEQ ID NO:2) or an amino acid sequence functionally similar to that sequence, and DNA sequences encoding such a receptor.
This invention provides an isolated receptor having the amino acid sequence of FIG. 1 (SEQ ID NO:2) or substantially the same amino acid sequence as the amino acid sequence shown in FIG. 1 (SEQ ID NO:2) or an amino acid sequence functionally similar to that sequence, and DNA sequences encoding such a receptor.
A novel receptor, "LDL-receptor related protein-3" ("LRP-3"), is provided, along with encoding nucleic acid. The gene is associated with type 1 diabetes (insulin dependent diabetes mellitus), and experimental evidence provides indication that it is the IDDM susceptibility gene IDDM4. In various aspects the invention provides nucleic acid, including coding sequences, oligonucleotide primers and probes, polypeptides, pharmaceutical compositions, methods of diagnosis or prognosis, and other methods relating to and based on the gene, including methods of treatment of diseases in which the gene may be implicated, including autoimmune diseases, such as glomerulonephritis, diseases and disorders involving disruption of endocytosis and/or antigen presentation, diseases and disorders involving cytokine clearance and/or inflammation, viral infection, elevation of free fatty acids or hypercholesterolemia, osteoporosis, Alzheimer's disease, and diabetes.
In accordance with the present invention, there is provided an example of a novel class of nuclear receptor(s), termed the steroid X receptor (SXR). SXR is expressed almost exclusively in the liver, the primary site of xenobiotic and steroid catabolism. Unlike classical steroid receptors, SXR heterodimerizes with RXR and binds to directly repeated sequences related to the half-site, AGTTCA. SXR can activate transcription through response elements found in some steroid inducible P450 genes in response to a wide variety of natural and synthetic steroid hormones, including antagonists such as PCN--ideal properties for a "steroid sensing receptor" which mediates the physiological effect(s) of hormones. SXR represents the first new class of steroid receptors described since the identification of the mineralocorticoid receptor ten years ago. Also provided according to the invention are nucleic acid sequences encoding the above-identified receptors, as well as constructs and cells containing same, and probes derived therefrom. Furthermore, it has also been discovered that a wide variety of substrates modulate the transcription activating effects of invention receptors.
