Mammalian IAP gene family, primers, probes and detection methods

Abstract

Disclosed is substantially pure DNA encoding mammalian IAP polypeptides; and methods of using such DNA to express the IAP polypeptides in cells and animals to inhibit apoptosis. Also disclosed are conserved regions characteristic of the IAP family and primer and probes for the identification and isolation of additional IAP genes. In addition, methods for treating diseases and disorders involving apoptosis are provided.

1 . A method of treating a patient diagnosed with cancer, the method comprising: administering to the patient an effective amount of a compound that inhibits the biological activity of XIAP polypeptide.  
     
     
         2 . The method, according to  claim 1 , in which the compound is a negative regulator of XIAP anti-apoptotic pathway.  
     
     
         3 . The method, according to  claim 1 , in which the compound is a compound that prevents cleavage of the XIAP polypeptide.  
     
     
         4 . The method, according to  claim 1 , in which the biological activity is the level of expression of the XIAP polypeptide.  
     
     
         5 . The method, according to  claim 1 , in which the biological activity is the level of expression of an mRNA molecule encoding the XIAP polypeptide.  
     
     
         6 . The method, according to  claim 1 , in which the biological activity is an apoptosis-inhibiting activity.  
     
     
         7 . The method, according to  claim 1 , in which the patient is a human.  
     
     
         8 . The method, according to  claim 1 , in which the cancer is selected from the group consisting of: promyelocytic leukemia, a HeLa-type carcinoma, chronic myelogenous leukemia, lymphoblastic leukemia, Burkitt's lymphoma, colorectal adenocarcinoma, lung carcinoma, and melanoma.  
     
     
         9 . The method, according to  claim 1 , in which the cancer is in a tissue selected from the group consisting of: ovary, lymph node. Skin, blood, lung, prostate, colon, rectum, testes, and small intestine.  
     
     
         10 . The method, according to  claim 1 , in which the XIAP polypeptide comprises a domain having at least 80% sequence identity to a BIR domain selected from the group consisting of amino acids 26-93 of human X-linked IAP (XIAP, SEQ ID NO: 4), amino acids 163-230 of human X-linked IAP (XIAP, SEQ ID NO: 4), and amino acids 265-330 of human X-linked IAP (XIAP, SEQ ID NO: 4).  
     
     
         11 . The method, according to  claim 10 , in which the polypeptide comprises a domain having at least 85% sequence identity to the BIR domain.  
     
     
         12 . The method, according to  claim 10  in which the polypeptide comprises a domain having at least 90% sequence identity to the BIR domain.  
     
     
         13 . The method, according to  claim 10  in which the polypeptide comprises a domain having at least 95% sequence identity to the BIR domain.  
     
     
         14 . The method, according to  claim 10 , in which the polypeptide comprises a BIR domain selected from the group consisting of amino acids 26-93 of human X-linked IAP (XIAP, SEQ ID NO: 4), amino acids 163-230 of human X-linked IAP (XIAP, SEQ ID NO: 4), and amino acids 265-330 of human X-linked IAP (XIAP, SEQ ID NO: 4).  
     
     
         15 . A method of treating a patient diagnosed with cancer, the method comprising: administering to the patient an effective amount of a compound that binds XIAP polypeptide.  
     
     
         16 . The method, according to  claim 15 , in which the compound is a negative regulator of XIAP anti-apoptotic pathway.  
     
     
         17 . The method, according to  claim 15 , in which the compound is a compound that prevents cleavage of the XIAP polypeptide.  
     
     
         18 . The method, according to  claim 15 , in which the biological activity is the level of expression of the XIAP polypeptide.  
     
     
         19 . The method, according to  claim 15 , in which the biological activity is the level of expression of an mRNA molecule encoding the XIAP polypeptide.  
     
     
         20 . The method, according to  claim 15 , in which the biological activity is an apoptosis-inhibiting activity.  
     
     
         21 . The method, according to  claim 15 , in which the patient is a human.  
     
     
         22 . The method, according to  claim 15 , in which the cancer is selected from the group consisting of: promyelocytic leukemia, a HeLa-type carcinoma, chronic myelogenous leukemia, lymphoblastic leukemia, Burkitt's lymphoma, colorectal adenocarcinoma, lung carcinoma, and melanoma.  
     
     
         23 . The method, according to  claim 15 , in which the cancer is in a tissue selected from the group consisting of: ovary, lymph node. Skin, blood, lung, prostate, colon, rectum, testes, and small intestine.  
     
     
         24 . The method, according to  claim 15 , in which the XIAP polypeptide comprises a domain having at least 80% sequence identity to a BIR domain selected from the group consisting of amino acids 26-93 of human X-linked IAP (XIAP, SEQ ID NO: 4), amino acids 163-230 of human X-linked IAP (XIAP, SEQ ID NO: 4), and amino acids 265-330 of human X-linked IAP (XIAP, SEQ ID NO: 4).  
     
     
         25 . The method, according to  claim 24 , in which the polypeptide comprises a domain having at least 85% sequence identity to the BIR domain.  
     
     
         26 . The method, according to  claim 24  in which the polypeptide comprises a domain having at least 90% sequence identity to the BIR domain.  
     
     
         27 . The method, according to  claim 24  in which the polypeptide comprises a domain having at least 95% sequence identity to the BIR domain.  
     
     
         28 . The method, according to  claim 24 , in which the polypeptide comprises a BIR domain selected from the group consisting of amino acids 26-93 of human X-linked IAP (XIAP, SEQ ID NO: 4), amino acids 163-230 of human X-linked IAP (XIAP, SEQ ID NO: 4), and amino acids 265-330 of human X-linked IAP (XIAP, SEQ ID NO: 4).