Novel human LXRalpha variants

Abstract

This invention provides novel human LXRα variant polypeptides and nucleic acids encoding such polypeptides. This invention also provides the therapeutic, diagnostic, and research utilities as well as the production of such polynucleotides and polypeptides. It is emphasized that this abstract is provided to comply with the rules requiring an abstract that will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims.

1 . An isolated nucleic acid molecule selected from the group consisting of: 
 (a) an isolated nucleic acid molecule encoding SEQ ID NO:6, 8, or 19; or    (b) an isolated nucleic acid molecule that hybridizes with the isolated nucleic acid molecule of (a) under hybridization conditions of 6×SSC (1M NaCl), 50% formamide, 1% SDS at 42° C., and a wash in 1×SSC at 42° C., and a wash at 68° C., in 0.2×SSC, and 0.1% SDS, wherein the nucleic acid molecule complementary to the isolated nucleic acid molecule that hybridizes with the isolated nucleic acid molecule of (a) encodes a polypeptide that has LXR-responsive pathway activity; and    (d) an isolated nucleic acid molecule that is complementary to (a) or (b).    
     
     
         2 . The isolated nucleic acid molecule of  claim 1  consisting of SEQ ID NO:5, 7, or 18.  
     
     
         3 . The isolated nucleic acid molecule of  claim 1 , wherein the isolated nucleic acid molecule is a DNA molecule.  
     
     
         4 . The isolated nucleic acid molecule of  claim 1 , wherein the isolated nucleic acid molecule is an RNA molecule.  
     
     
         5 . The isolated nucleic acid molecule of claim  1 (b), wherein the isolated nucleic acid molecule comprises SEQ ID NO:5, 7, or 18.  
     
     
         6 . (canceled)  
     
     
         7 . The nucleic acid molecule of  claim 1 , wherein the polypeptide encoded by the isolated nucleic acid molecule can form a dimer with a wild-type LXRα.  
     
     
         8 . The nucleic acid molecule of  claim 1 , wherein the polypeptide encoded by the isolated nucleic acid molecule can form a heterodimer with a retinoid X receptor (RXR).  
     
     
         9 . The nucleic acid molecule of  claim 8 , wherein the RXR is an RXRα, RXRβ, or RXRγ.  
     
     
         10 . A polypeptide encoded by the isolated nucleic acid molecule of  claim 1 .  
     
     
         11 . The polypeptide of  claim 10 , wherein the polypeptide can form a dimer with a wild-type LXRα.  
     
     
         12 . The polypeptide of  claim 10 , wherein the polypeptide can form a heterodimer with an RXR.  
     
     
         13 . The polypeptide of  claim 12 , wherein formation of the heterodimer can inhibit formation of a heterodimer between the RXR and a nuclear receptor with which the RXR naturally heterodimerizes.  
     
     
         14 . The polypeptide of  claim 12 , wherein formation of the heterodimer can inhibit formation of a homodimer of the RXR.  
     
     
         15 . The polypeptide of  claim 12 , wherein, RXR is an RXRα, RXRβ, or RXRγ.  
     
     
         16 . The polypeptide of  claim 10 , wherein the polypeptide can exhibit LXRα dominant negative activity.  
     
     
         17 . The polypeptide of  claim 12 , wherein the LXRα variant is a fragment of an LXRα-64, an LXRα-42 + , or an LXRα-42 − .  
     
     
         18 . The polypeptide of  claim 17 , wherein the fragment of an LXRα variant can exhibit at least one function of an LXRα variant.  
     
     
         19 . A construct comprising an isolated nucleic acid molecule of  claim 1 .  
     
     
         20 . The construct of  claim 19 , wherein the isolated nucleic acid molecule is operatively linked to a regulatory sequence.  
     
     
         21 . The construct of  claim 19 , wherein the construct is a plasmid.  
     
     
         22 . The construct of  claim 19 , wherein the construct comprises pCMV/myc or pcDNA 3.1, or is a derivative thereof.  
     
     
         23 . A host cell comprising an isolated nucleic acid molecule of  claim 1  or a descendent of the cell.  
     
     
         24 . A host cell comprising the construct of  claim 19 .  
     
     
         25 . The host cell of  claim 23 , wherein the host cell is a prokaryotic cell.  
     
     
         26 . The host cell of  claim 23 , wherein the host cell is an  E. coli.    
     
     
         27 . The host cell of  claim 23 , wherein the host cell is a mammalian cell.  
     
     
         28 . The host cell of  claim 23 , wherein the host cell is a human cell.  
     
     
         29 . The host cell of  claim 23 , wherein the host cell is a human embryonic cell.  
     
     
         30 . The host cell of  claim 23 , wherein the host cell is selected from the group consisting of a human hepatoma cell (HepG2), a Chinese hamster ovary cell (CHO), a monkey COS-1 cell, and a human embryonic kidney cell (HEK 293).  
     
     
         31 . The host cell of  claim 23 , wherein, the host cell is selected from the group consisting of a  Saccharomyces cerevisiae  cell, a  Schizosaccharomyces pombe  cell, and a  Pichia pastoris  cell.  
     
     
         32 - 77 . (canceled)