XAF genes and polypeptides: methods and reagents for modulating apoptosis

Abstract

The invention provides novel XAF nucleic acid sequences. Also provided are XAF polypeptides, anti-XAF antibodies, and methods for modulating apoptosis and detecting compounds which modulate apoptosis.

1 . A method of treating a patient diagnosed as having a condition involving insufficient apoptosis, said method comprising providing said patient with a polypeptide, said polypeptide comprising at least 85% amino acid sequence identity to SEQ ID NO:2, 4, 10, or 12, or a fragment thereof, said polypeptide having XAF biological activity, said providing in an amount sufficient to increase apoptosis in a cell of said patient.  
     
     
         2 . The method of  claim 1 , wherein said patient is a human.  
     
     
         3 . The method of  claim 1 , wherein said polypeptide is in a pharmaceutically acceptable carrier.  
     
     
         4 . The method of  claim 3 , wherein said carrier is a liquid solution or suspension.  
     
     
         5 . The method of  claim 3 , wherein said carrier is in the form of a tablet or capsule.  
     
     
         6 . The method of  claim 3 , wherein said carrier is suitable for parenteral, intravenous, intra-arterial, subcutaneous, intramuscular, intracranial, intraorbital, ophthalmic, intraventricular, intracapsular, intraspinal, intracisternal, intraperitoneal, intranasal, or oral administration.  
     
     
         7 . The method of  claim 1 , wherein said polypeptide comprises at least 85% amino acid sequence identity to SEQ ID NO:2, or a fragment thereof having XAF activity.  
     
     
         8 . The method of  claim 7 , wherein said polypeptide comprises the amino acid sequence of SEQ ID NO:2.  
     
     
         9 . The method of  claim 1 , wherein said polypeptide comprises at least 85% amino acid sequence identity to SEQ ID NO:4, or a fragment thereof having XAF activity.  
     
     
         10 . The method of  claim 9 , wherein said polypeptide comprises the amino acid sequence of SEQ ID NO:4.  
     
     
         11 . The method of  claim 1 , wherein said polypeptide comprises at least 85% amino acid sequence identity to SEQ ID NO: 10, or a fragment thereof having XAF activity.  
     
     
         12 . The method of  claim 11 , wherein said polypeptide comprises the amino acid sequence of SEQ ID NO: 10.  
     
     
         13 . The method of  claim 1 , wherein said polypeptide comprises at least 85% amino acid sequence identity to SEQ ID NO:12, or a fragment thereof having XAF activity.  
     
     
         14 . The method of  claim 13 , wherein said polypeptide comprises the amino acid sequence of SEQ ID NO:12.  
     
     
         15 . The method of  claim 1 , wherein said condition is breast cancer, uterine cervical carcinoma, gastric carcinoma, ovarian epithelial cancer, pediatric medulloblastoma, lung carcinoma, or prostate cancer.  
     
     
         16 . The method of  claim 1 , wherein said providing is parenteral, intravenous, intra-arterial, subcutaneous, intramuscular, intracranial, intraorbital, ophthalmic, intraventricular, intracapsular, intraspinal, intracisternal, intraperitoneal, intranasal, by suppositories, or oral.  
     
     
         17 . The method of  claim 1 , wherein said cell is a peripheral blood leukocyte, a muscle cell, an intestinal cell, an ovarian cell, a placental cell, or a thymus cell.  
     
     
         18 . The method of  claim 17 , wherein said peripheral blood leukocyte is a lymphocyte.  
     
     
         19 . The method of  claim 17 , wherein said muscle cell is a myocardial cell.  
     
     
         20 . The method of  claim 17 , wherein said thymus cell is a thymocyte.  
     
     
         21 . The method of  claim 1 , wherein said XAF biological activity is selected from the group consisting of the ability to bind an IAP, the ability to bind another XAF polypeptide, the ability to cause apoptosis when introduced into a cell, the ability to enhance the NF-κB inducing activity of a TRAF, and the ability to bind a XAF-1, XAF02L, or XAF-2S specific antibody.