DNA encoding a novel human inhibitor-of-apoptosis protein

Abstract

The present invention relates to novel human inhibitor-of-apoptosis polypeptides, designated HIAP3, polynucleotides encoding the polypeptides, methods for producing the polypeptides, expression vectors and genetically engineered host cells for expression of the polypeptides. The invention further relates to methods for utilizing the polynucleotides and polypeptides in research, diagnosis, and therapeutic applications.

What is claimed is:  
     
         1 . An isolated polynucleotide comprising a polynucleotide having at least a 70% identity to a member selected from the group consisting of: 
 (a) a polynucleotide encoding a polypeptide comprising the amino acid sequence set forth in FIG. 2;    (b) a polynucleotide encoding a polypeptide comprising amino acid 88 to amino acid 289 as set forth in FIG. 2;    (c) a polynucleotide encoding a polypeptide comprising amino acid 88 to amino acid 155 as set forth in FIG. 2;    (d) a polynucleotide encoding a polypeptide comprising amino acid 240 to amino acid 289 as set forth in FIG. 2; and    (e) polynucleotide which is complementary to the polynucleotide of (a), (b), (c) or (d).    
     
     
         2 . The polynucleotide of  claim 1  wherein the polynucleotide is DNA.  
     
     
         3 . The polynucleotide of  claim 1  wherein the polynucleotide is RNA.  
     
     
         4 . The polynucleotide of  claim 1  wherein the polynucleotide is genomic DNA.  
     
     
         5 . The polynucleotide of  claim 2  wherein the polynucleotide encodes the polypeptide comprising amino acids 1 to 298 as set forth in FIG. 2.  
     
     
         6 . The polynucleotide of  claim 2  wherein the polynucleotide encodes the polypeptide comprising amino acid 88 to amino acid 289 as set forth in FIG. 2.  
     
     
         7 . The polynucleotide of  claim 2  wherein the polynucleotide encodes the polypeptide comprising amino acid 88 to amino acid 155 as set forth in FIG. 2.  
     
     
         8 . The polynucleotide of  claim 2  wherein the polynucleotide encodes the polypeptide comprising amino acid 240 to amino acid 289 as set forth in FIG. 2.  
     
     
         9 . The polynucleotide of  claim 1  wherein the polynucleotide comprises the sequence as set forth in FIG. 1 from nucleotide 1 to nucleotide 1337.  
     
     
         10 . The polynucleotide of  claim 1  wherein the polynucleotide comprises the sequence as set forth in FIG. 1 from nucleotide 170 to nucleotide 1064.  
     
     
         11 . An vector comprising the polynucleotide of  claim 2 .  
     
     
         12 . A host cell comprising the vector of  claim 11 .  
     
     
         13 . A method of producing a polypeptide comprising expressing from the host cell of  claim 12  the polypeptide encoded by the polynucleotide.  
     
     
         14 . The method of  claim 13  wherein the polypeptide comprises amino acid 1 to amino acid 298 as set forth in FIG. 2.  
     
     
         15 . The method of  claim 13  wherein the polypeptide comprises amino acid 88 to amino acid 289 as set forth in FIG. 2.  
     
     
         16 . The method of  claim 13  wherein the polypeptide comprises amino acid 88 to amino acid 155 as set forth in FIG. 2.  
     
     
         17 . The method of  claim 13  wherein the polypeptide comprises amino acid 240 to amino acid 289 as set forth in FIG. 2.  
     
     
         18 . A method of producing a polypeptide wherein the polypeptide comprises the amino acid sequence shown in FIG. 2, the method comprising the steps of: 
 (a) culturing the host cell of  claim 12  under conditions whereby the polypeptide is expressed; and    (b) recovering the polypeptide from the culture.    
     
     
         19 . A method for producing a cell which expresses a polypeptide comprising genetically engineering the cell with the vector of  claim 11 .  
     
     
         20 . A polypeptide comprising a member selected from the group consisting of: 
 (a) a polypeptide having the amino acid sequence as set forth in FIG. 2;    (b) a polypeptide comprising amino acid 88 to amino acid 289 as set forth in FIG. 2;    (c) a polypeptide comprising amino acid 88 to amino acid 155 as set forth in FIG. 2;    (d) a polypeptide comprising amino acid 240 to amino acid 289 as set forth in FIG. 2; and    (e) a polypeptide which is at least 70% identical to the polypeptide of (a), (b), (c) or (d).    
     
     
         21 . The polypeptide of  claim 20  wherein the polypeptide comprises amino acid 1 to amino acid 298 as set forth in FIG. 2.  
     
     
         21 . The polypeptide of  claim 20  wherein the polypeptide comprises amino acid 88 to amino acid 289 as set forth in FIG. 2.  
     
     
         22 . The polypeptide of  claim 20  wherein the polypeptide comprises amino acid 88 to amino acid 155 as set forth in FIG. 2.  
     
     
         23 . The polypeptide of  claim 20  wherein the polypeptide comprises amino acid 240 to amino acid 289 as set forth in FIG. 2  
     
     
         24 . A method of treating a disease-state in a human patient which disease-state is associated with inappropriate apoptosis and wherein the patient is in need of increased levels of a polypeptide comprising a member selected from the group consisting of: 
 (a) a polypeptide having the amino acid sequence as set forth in FIG. 2;    (b) a polypeptide comprising amino acid 88 to amino acid 289 as set forth in FIG. 2;    (c) a polypeptide comprising amino acid 88 to amino acid 155 as set forth in FIG. 2;    (d) a polypeptide comprising amino acid 240 to amino acid 289 as set forth in FIG. 2; and    (e) a polypeptide which is at least 70% identical to the polypeptide of (a), (b), (c) or (d);    wherein the method comprises administering to the patient a therapeutically effective amount of the polypeptide.    
     
     
         25 . The method of  claim 24  wherein said therapeutically effective amount of the polypeptide is administered by providing to the patient a polynucleotide encoding the polypeptide and expressing the polypeptide in vivo.  
     
     
         26 . A method of treating a disease-state in a human patient which disease-state is associated with inappropriate apoptosis and wherein the patient is in need of decreased levels of a polypeptide comprising a member selected from the group consisting of: 
 (a) a polypeptide having the amino acid sequence as set forth in FIG. 2;    (b) a polypeptide comprising amino acid 88 to amino acid 289 as set forth in FIG. 2;    (c) a polypeptide comprising amino acid 88 to amino acid 155 as set forth in FIG. 2;    (d) a polypeptide comprising amino acid 240 to amino acid 289 as set forth in FIG. 2; and    (e) a polypeptide which is at least 70% identical to the polypeptide of (a), (b), (c) or (d);    wherein the method comprises administering to the patient a therapeutically effective amount of a ribozyme which specifically cleaves RNA encoding the polypeptide.    
     
     
         27 . A method of treating a disease-state in a human patient which disease-state is associated with inappropriate apoptosis and wherein the patient is in need of decreased levels of a polypeptide comprising a member selected from the group consisting of: 
 (a) a polypeptide having the amino acid sequence as set forth in FIG. 2;    (b) a polypeptide comprising amino acid 88 to amino acid 289 as set forth in FIG. 2;    (c) a polypeptide comprising amino acid 88 to amino acid 155 as set forth in FIG. 2;    (d) a polypeptide comprising amino acid 240 to amino acid 289 as set forth in FIG. 2; and    (e) a polypeptide which is at least 70% identical to the polypeptide of (a), (b), (c) or (d);    awherein the method comprises administering to the patient a therapeutically effective amount of a polynucleotide which is complementary to a polynucleotide encoding the polypeptide.    
     
     
         28 . A diagnostic method wherein the method comprises analyzing for the presence of a polypeptide comprising a member selected from the group consisting of: 
 (a) a polypeptide having the amino acid sequence as set forth in FIG. 2;    (b) a polypeptide comprising amino acid 88 to amino acid 289 as set forth in FIG. 2;    (c) a polypeptide comprising amino acid 88 to amino acid 155 as set forth in FIG. 2;    (d) a polypeptide comprising amino acid 240 to amino acid 289 as set forth in FIG. 2; and    (e) a polypeptide which is at least 70% identical to the polypeptide of (a), (b), (c) or (d);    in a sample derived from a host.    
     
     
         29 . A diagnostic method wherein the method comprises analyzing for the presence of a polynucleotide comprising a polynucleotide having at least 70% identity to a member selected from the group consisting of: 
 (a) a polynucleotide encoding a polypeptide comprising the amino acid sequence set forth in FIG. 2;    (b) a polynucleotide encoding a polypeptide comprising amino acid 88 to amino acid 289 as set forth in FIG. 2;    (c) a polynucleotide encoding a polypeptide comprising amino acid 88 to amino acid 155 as set forth in FIG. 2;    (d) a polynucleotide encoding a polypeptide comprising amino acid 240 to amino acid 289 as set forth in FIG. 2; and    (e) polynucleotide which is complementary to the polynucleotide of (a), (b), (c) or (d);    in a sample derived from a host.    
     
     
         30 . An isolated antibody which is specific for a polypeptide comprising a member selected from the group consisting of: 
 (a) a polypeptide having the amino acid sequence as set forth in FIG. 2;    (b) a polypeptide comprising amino acid 88 to amino acid 289 as set forth in FIG. 2;    (c) a polypeptide comprising amino acid 88 to amino acid 155 as set forth in FIG. 2;    (d) a polypeptide comprising amino acid 240 to amino acid 289 as set forth in FIG. 2; and    (e) a polypeptide which is at least 70% identical to the polypeptide of (a), (b), (c) or (d).