RAIDD, a novel death adaptor molecule

Abstract

The present invention relates to a novel molecule involved in the process of apoptosis. In particular, isolated nucleic acid molecules are provided encoding the human RAIDD protein and splice variants thereof—referred to as RAIDD-SV1 and RAIDD-SV2. RAIDD polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of RAIDD activity.

What is claimed is:  
     
         1 . An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of: 
 (a) a nucleotide sequence encoding a polypeptide comprising amino acids from about 1 to about 199 in SEQ ID NO:2;    (b) a nucleotide sequence encoding a polypeptide comprising amino acids from about 2 to about 199 in SEQ ID NO:2;    (c) a nucleotide sequence encoding a polypeptide comprising amino acids from about 8 to about 80 in SEQ ID NO:2;    (d) a nucleotide sequence encoding a polypeptide comprising amino acids from about 123 to about 194 in SEQ ID NO:2;    (e) a nucleotide sequence encoding a polypeptide comprising amino acids from about 99 to about 199 in SEQ I) NO:2;    (f) a nucleotide sequence encoding a polypeptide comprising amino acids from about 118 to about 199 in SEQ ID NO:2;    (g) a nucleotide sequence encoding a polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97824; and    (h) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d), (e), (f), or (g).    
     
     
         2 . An isolated nucleic acid molecule comprising a polynucleotide which hybridizes under stringent hybridization conditions to a polynucleotide having a nucleotide sequence identical to a nucleotide sequence in (a), (b), (c), (d), (e), (f), (g), or (h) of  claim 1  wherein said polynucleotide which hybridizes does not hybridize under stringent hybridization conditions to a polynucleotide having a nucleotide sequence consisting of only A residues or of only T residues.  
     
     
         3 . A method for making a recombinant vector comprising inserting an isolated nucleic acid molecule of  claim 1  into a vector.  
     
     
         4 . A recombinant vector produced by the method of  claim 3 .  
     
     
         5 . A method of making a recombinant host cell comprising introducing the recombinant vector of  claim 4  into a host cell.  
     
     
         6 . A recombinant host cell produced by the method of  claim 5 .  
     
     
         7 . A recombinant method for producing a RAIDD polypeptide, comprising culturing the recombinant host cell of  claim 6  under conditions such that said polypeptide is expressed and recovering said polypeptide.  
     
     
         8 . An isolated RAIDD polypeptide having an amino acid sequence at least 95% identical to a sequence selected from the group consisting of: 
 (a) amino acids from about 1 to about 199 in SEQ ID NO:2;    (b) amino acids from about 2 to about 199 in SEQ ID NO:2;    (c) amino acids from about 8 to about 80 in SEQ ID NO:2;    (d) amino acids from about 123 to about 194 in SEQ ID NO:2;    (e) amino acids from about 99 to about 199 in SEQ ID NO:2;    (f) amino acids from about 118 to about 199 in SEQ ID NO:2;    (g) the amino acid sequence of the RAIDD polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97824; and    (h) the amino acid sequence of an epitope-bearing portion of any one of the polypeptides of (a), (b), (c), (d), (e), (f), or (g).    
     
     
         9 . An isolated antibody that binds specifically to a RAIDD polypeptide of  claim 8 .  
     
     
         10 . A method for identifying agonists and antagonists of RAIDD induced cell death comprising: 
 (a) contacting cells which express a RAIDD polypeptide with a candidate molecule, and    (b) measuring the level of RAIDD induced cell death; whereby, an increased level of RAIDD induced cell death compared to a standard level of RAIDD induced cell death indicates that said candidate molecule is an agonist and a decreased level of RAIDD induced cell death compared to said standard indicates that said candidate molecule is an antagonist.