Lifeguard (LFG) polynucleotides and polypeptides and methods of use thereof

Abstract

A substantially purified lifeguard (LFG) polypeptide is provided. The polypeptide includes an amino acid sequence as set forth in SEQ ID NO: 2, or a conservative variant thereof. An isolated polynucleotide is provided that encodes an amino acid sequence as set forth in SEQ ID NO: 2, or a conservative variant thereof. An antibody is provided that binds to a polypeptide having an amino acid sequence as set forth in SEQ ID NO: 2. A method is provided for identifying a compound which affects a function of a polypeptide as set forth in SEQ ID NO: 2, or a conservative variant thereof, or affects the expression of a polynucleotide comprising a sequence as set forth in SEQ ID NO: 1. A method is provided for treating a subject with a disorder associated with decreased or increased Fas-mediated cell death. A method is provided for treating a patient having or at risk of having a disorder associated with increased Fas-mediated cell death.

What is claimed is:  
     
         1 . An antibody which binds to a polypeptide having an amino acid sequence as set forth in SEQ ID NO: 2.  
     
     
         2 . The antibody of  claim 1 , wherein the antibody is monoclonal.  
     
     
         3 . The antibody of  claim 1 , wherein the antibody is polyclonal.  
     
     
         4 . A method of screening for a compound which affects apoptosis, comprising: 
 (a) incubating the compound and a cell expressing a polypeptide having the amino acid sequence of SEQ ID NO: 2, or a conservative variant thereof, under conditions sufficient to allow the compound to interact with the cell;    (b) determining the effect of the compound on apoptosis; and    (c) comparing apoptotic death of said cell contacted with said compound with apoptotic cell death of a cell not contacted with said compound.    
     
     
         5 . The method of  claim 4 , wherein said cell is a host cell containing an expression vector comprising an isolated polynucleotide encoding SEQ ID NO: 2 or a conservative variant thereof.  
     
     
         6 . The method of  claim 4 , wherein the effect is inhibition of a function of a polypeptide comprising a sequence as set forth as SEQ ID NO: 2 or a conservative variant thereof, or a decrease of expression of a nucleic acid comprising a sequence as set forth as SEQ ID NO: 1.  
     
     
         7 . The method of  claim 4 , wherein the effect is augmentation of a function of a polypeptide comprising a sequence as set forth as SEQ ID NO: 2 or a conservative variant thereof, or a decrease of expression of a nucleic acid comprising a sequence as set forth as SEQ ID NO: 1.  
     
     
         8 . A method of treating a subject with a disorder associated with decreased Fas-mediated cell death, comprising administering to the subject a therapeutically effective amount of a compound that inhibits the function of a protein having the amino acid sequence of SEQ ID NO: 2.  
     
     
         9 . A method of treating a subject with a disorder associated with increased Fas-mediated cell death, comprising administering to the subject a therapeutically effective of a compound that augments the function of a protein having the amino acid sequence of SEQ ID NO: 2 or a conservative variation thereof.  
     
     
         10 . The method of  claim 9 , wherein said cell disorder is a cellular accumulation disorder.  
     
     
         11 . The method of  claim 10 , wherein said disorder is rheumatoid arthritis.  
     
     
         12 . The method of  claim 9 , wherein said compound is a therapeutically effective amount of a polypeptide of SEQ ID NO: 2.  
     
     
         13 . The method of  claim 9 , wherein said compound is a therapeutically effective amount of a polynucleotide encoding SEQ ID NO: 2.  
     
     
         14 . A method of treating a patient having or at risk of having a disorder associated with increased Fas-mediated cell death, comprising: 
 identifying a patent at risk for said disorder; and    introducing into a cell of a patient having a disorder associated with Fas-mediated cell death a polynucleotide sequence encoding the amino acid sequence of SEQ ID NO: 2 operatively linked to a promoter, thereby inhibiting Fas-mediated cell death.    
     
     
         15 . A kit for detecting the presence of LFG in a sample, the kit comprising carrier means being compartmentalized to receive therein one or more containers comprising a container containing an antibody which specifically binds to a protein having the amino acid sequence of SEQ ID NO: 2.  
     
     
         16 . A kit useful for the detection of a target LFG nucleic acid sequence, the kit comprising carrier means being compartmentalized to receive therein one or more containers comprising a container containing oligonucleotides which hybridize to a nucleic acid having the nucleotide sequence of SEQ ID NO: 1.  
     
     
         17 . A transgenic nonhuman animal having a phenotype characterized by expression of LFG, otherwise not naturally occurring in the animal, the phenotype being conferred by a transgene contained in the somatic and germ cells of the animal, the transgene comprising a nucleic acid sequence which encodes the amino acid sequence of SEQ ID NO: 2.  
     
     
         18 . The transgenic animal of  claim 17 , wherein said animal exhibits a phenotype characterized by decreased Fas-mediated cell death resulting in a cellular accumulation.  
     
     
         19 . The transgenic nonhuman animal of  claim 17 , wherein the animal is a mouse.