Modulators of the function of FAS/APO1 receptors

Abstract

The MORT-1 protein, analogs thereof and fragments thereof bind with the intracellular domain of the FAS ligand receptor. DNA encoding such protein, analogs and fragments, may be used to make vectors and host cells in order to produce such proteins, analogs and fragments. The peptides may be formulated into pharmaceutical compositions for use in modulation of the FAS-R ligand effect on cells carrying a FAS-R.

What is claimed is:  
     
         1 . A DNA molecule comprising: 
 (1) a DNA sequence which encodes the MORT-1 protein, having the amino acid sequence of SEQ ID NO:2;    (2) a DNA sequence which encodes an analog of said MORT-1 protein which binds with the intracellular domain of the FAS ligand receptor (FAS-IC), which DNA sequence is capable of hybridization to the cDNA encoding SEQ ID NO:2 under moderately stringent conditions; or (3) a DNA coding sequence consisting of a DNA sequence which encodes a fragment of said MORT-1 protein which binds with FAS-IC.    
     
     
         2 . A DNA molecule in accordance with  claim 1 , comprising a DNA sequence encoding an analog of said MORT-1 protein which binds with FAS-IC, which DNA sequence is capable of hybridization to the cDNA encoding SEQ ID NO:2 under moderately stringent conditions.  
     
     
         3 . A vector comprising a DNA sequence according to  claim 1 .  
     
     
         4 . A vector according to  claim 3  which is capable of being expressed in a eukaryotic host cell.  
     
     
         5 . A vector according to  claim 3  which is capable of being expressed in a prokaryotic host cell.  
     
     
         6 . Transformed eukaryotic or prokaryotic host cells containing a vector according to  claim 3 .  
     
     
         7 . A method for producing a polypeptide which binds to the intracellular domain of the FAS-R, comprising growing the transformed host cells according to  claim 6  under conditions suitable for the expression of an expression product from said cells, effecting post-translational modifications of said expression product as necessary for obtention of said polypeptide, and isolating said expressed polypeptide.  
     
     
         8 . A polypeptide comprising: 
 (1) the MORT-1 protein having the amino acid sequence of SEQ ID NO:2;    (2) an analog of said MORT-1 protein which binds with the intracellular domain of the FAS ligand receptor (FAS-IC), which analog is encoded by a DNA sequence which is capable of hybridization to the cDNA encoding SEQ ID NO:2 under moderately stringent conditions; or (3) a fragment of said MORT-1 protein which binds with FAS-IC.    
     
     
         9 . A polypeptide in accordance with  claim 8 , comprising an analog of said MORT-1 protein which binds with FAS-IC, which analog is encoded by a DNA sequence capable of hybridization to the cDNA encoding SEQ ID NO:2 under moderately stringent conditions.  
     
     
         10 . A pharmaceutical composition for the modulation of the FAS-R ligand-effect on cells comprising, as active ingredient, a polypeptide according to  claim 8 .  
     
     
         11 . A pharmaceutical composition for modulating the FAS-R ligand-effect on cells comprising, as active ingredient, a recombinant animal virus vector encoding a protein capable of binding a cell surface receptor and encoding a polypeptide according to  claim 8 .  
     
     
         12 . A method for the modulation of the FAS-R ligand effect on cells carrying a FAS-R, comprising treating said cells with one or more polypeptides according to  claim 8 , capable of binding to the intracellular domain and modulating the activity of said FAS-R, wherein said treating of said cells comprises introducing into said cells said one or more polypeptides in a form suitable for intracellular introduction thereof, or introducing into said cells a DNA sequence encoding said one or more polypeptides in the form of a suitable vector carrying said sequence, said vector being capable of effecting the insertion of said sequence into said cells in a way that said sequence is expressed in said cells.  
     
     
         13 . A method for modulation of the FAS-R ligand-effect on cells according to  claim 12 , comprising treating said cells with a single said polypeptide.