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 increasing apoptosis in a cell, said method comprising administering to said cell an apoptosis inducing amount of XAF polypeptide or fragment thereof.  
     
     
         2 . A method of increasing apoptosis in a mammal, said method comprising providing a transgene encoding a XAF polypeptide or fragment thereof to a cell of said mammal, said transgene being positioned for expression in said cell.  
     
     
         3 . A method of increasing apoptosis in a cell, said method comprising administering a compound which increases XAF biological activity.  
     
     
         4 . The method of  claim 3 , wherein said compound selected from a group consisting of a polypeptide fragment of a XAF polypeptide, a mutant of a XAF polypeptide, and a nucleic acid encoding a XAF polypeptide, a mutant thereof, or a polypeptide fragment thereof.  
     
     
         5 . The method of  claim 1 ,  2 , or  3 , wherein said XAF is selected from a group consisting of XAF-1, XAF-2 N-terminus, XAF-2L, and XAF-2S.  
     
     
         6 . The method of  claim 1 ,  2 , or  3 , wherein said XAF is from a mammal.  
     
     
         7 . The method of  claim 1 ,  2 , or  3 , wherein said cell is in a mammal.  
     
     
         8 . The method of  claim 6  or  7 , wherein said mammal is selected from a group consisting of a human and a rodent.  
     
     
         9 . The method of  claim 1 ,  2 , or  3 , wherein said cell is in a mammal diagnosed as having a condition involving insufficient apoptosis.  
     
     
         10 . The method of  claim 9 , wherein said condition is cancer.  
     
     
         11 . The method of  claim 10 , wherein said cancer is selected from a group consisting of breast cancer, uterine cervical carcinoma, gastric carcinoma, ovarian epithelial cancer, pediatric medulloblastoma, lung carcinoma, and prostate cancer.  
     
     
         12 . The method of  claim 1 ,  2 , or  3 , wherein said cell is selected from a group consisting of a peripheral blood leukocyte, a muscle cell, a myocardial cell, an intestinal cell, an ovarian cell, a placental cell, and a thymus cell.  
     
     
         13 . The method of  claim 12 , wherein said thymus cell is a thymocyte.  
     
     
         14 . The method of  claim 12 , wherein said peripheral blood leukocyte is a lymphocyte.  
     
     
         15 . A method of inhibiting apoptosis in a cell, said method comprising administering to said cell an apoptosis inhibiting amount of XAF polypeptide or fragment thereof.  
     
     
         16 . A method of inhibiting apoptosis in a mammal, said method comprising providing a transgene encoding a XAF polypeptide or fragment thereof to a cell of said mammal, said transgene being positioned for expression in said cell.  
     
     
         17 . A method of inhibiting apoptosis in a cell, said method comprising administering a compound which decreases XAF biological activity.  
     
     
         18 . The method of  claim 17 , wherein said compound is selected from a group consisting of an antibody that specifically binds to XAF, a fragment of a XAF polypeptide, a mutant of a XAF polypeptide, a nucleic acid encoding a XAF polypeptide, a mutant thereof, or a polypeptide fragment thereof, a negative regulator of a XAF-dependent apoptotic pathway, and a XAF antisense nucleic acid.  
     
     
         19 . The method of  claim 18 , wherein said antibody is a neutralizing antibody.  
     
     
         20 . The method of  claim 15 ,  16 , or  17 , wherein said XAF is selected from a group consisting of XAF-1, XAF-2 N-terminus, XAF-2L, and XAF-2S.  
     
     
         21 . The method of  claim 15 ,  16 , or  17 , wherein said XAF is from a mammal.  
     
     
         22 . The method of  claim 15 ,  16 , or  17 , wherein said cell is in a mammal.  
     
     
         23 . The method of  claim 22 , wherein said mammal is selected from a group consisting of a human and a rodent.  
     
     
         24 . The method of  claim 15 ,  16 , or  17 , wherein said cell is in a mammal diagnosed as having a condition involving excessive apoptosis.  
     
     
         25 . The method of  claim 24 , wherein said condition is selected from a group consisting of AIDS, a neurodegenerative disease, a myelodysplastic syndrome, and an ischemic injury.  
     
     
         26 . The method of  claim 25 , wherein said ischemic injury is caused by a myocardial infarction, a stroke, a reperfusion injury, a toxin-induced liver disease, physical injury, renal failure, a secondary exsanguination or blood flow interruption resulting from any other primary diseases.  
     
     
         27 . The method of  claim 15 ,  16 , or  17 , wherein said cell is selected from a group consisting of a muscle cell, a myocardial cell, a peripheral blood leukocyte, an intestinal cell, an ovarian cell, a placental cell, and a thymus cell.  
     
     
         28 . The method of  claim 27 , wherein said peripheral blood leukocyte is a lymphocyte.  
     
     
         29 . The method of  claim 28 , wherein said lymphocyte is a T lymphocyte.  
     
     
         30 . The method of  claim 29 , wherein said T lymphocyte is CD4+.  
     
     
         31 . The method of  claim 27 , wherein said thymus cell is a thymocyte.