Novel death associated proteins, and thap1 and par4 pathways in apoptosis control

Abstract

The invention relates to genes and proteins of the THAP (THanatos (death)-Associated Protein) family comprising a THAP domain, and their use in diagnostics, treatment of disease, and in the identification of molecules for the treatment of disease. The invention also relates to the Par4 protein and SLC chemokine pathways, including the interaction of Par4 and SLC with THAP family proteins, and the recruitment and localization of Par4 to PML nuclear bodies.

1 . A method of ameliorating a condition associated with the activity of SLC in an individual comprising administering a polypeptide comprising the SLC binding domain of a THAP-family protein to said individual. 
     
     
         2 . The method of  claim 1 , wherein said polypeptide comprises a fusion protein comprising an Fc region of an immunoglobulin fused to a polypeptide comprising the amino acid sequence selected from the group consisting of amino acids 143-213 of SEQ ID NO: 3 and homologs thereof having at least 70% amino acid identity. 
     
     
         3 . The method of  claim 2 , wherein said amino acid identity is at least 80%. 
     
     
         4 . The method of  claim 3 , wherein said amino acid identity is at least 90%. 
     
     
         5 . The method of  claim 1 , wherein said polypeptide comprises an oligomeric THAP protein comprising a plurality of THAP polypeptides, wherein each THAP polypeptide comprises the amino acid sequence selected from the group consisting of amino acid 143-213 of SEQ ID NO: 3 and homologs thereof having at least 70% amino acid identity. 
     
     
         6 . The method of  claim 5 , wherein said amino acid identity is at least 80%. 
     
     
         7 . The method of  claim 6 , wherein said amino acid identity is at least 90%. 
     
     
         8 . The method of  claim 1 , wherein said condition is inflammation. 
     
     
         9 . The method of  claim 1 , wherein said polypeptide comprises SEQ ID NO: 3. 
     
     
         10 . The method of  claim 1 , wherein said polypeptide is a fragment of SEQ ID NO: 3. 
     
     
         11 . The method of  claim 10 , wherein said fragment comprises at least 60 consecutive amino acids of SEQ ID NO: 3. 
     
     
         12 . The method of  claim 10 , wherein said fragment comprises at least 70 consecutive amino acids of SEQ ID NO: 3. 
     
     
         13 . The method of  claim 10 , wherein said fragment comprises at least 80 consecutive amino acids of SEQ ID NO: 3. 
     
     
         14 . The method of  claim 1 , wherein said SLC binding domain comprises the amino acid sequence selected from the group consisting of amino acid 143-213 of SEQ ID NO: 3 and homologs thereof having at least 70% amino acid identity. 
     
     
         15 . The method of  claim 14 , wherein said amino acid identity is at least 80%. 
     
     
         16 . The method of  claim 15 , wherein said amino acid identity is at least 90%.