Novel molecules of the card-related protein family and uses thereof

Abstract

Novel CARD-9, CARD-10, or CARD-11 polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated CARD-9, CARD-10, or CARD-11 proteins, the invention further provides CARD-9, CARD-10, or CARD-1l, fusion proteins, antigenic peptides and anti-CARD-9, CARD-10, or CARD-11 antibodies. The invention also provides CARD-9, CARD-10, or CARD-11 nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which a CARD-9, CARD-10 or CARD-11 gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

What is claimed is:  
     
         1 . An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:8.  
     
     
         2 . The isolated nucleic acid molecule of  claim 1 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:8.  
     
     
         3 . An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising at least 25 contiguous amino acids of the amino acid sequence of SEQ ID NO:8.  
     
     
         4 . The isolated nucleic acid molecule of  claim 3 , wherein the polypeptide comprises at least 50 contiguous amino acids of the amino acid sequence of SEQ ID No:8.  
     
     
         5 . An isolated nucleic acid molecule comprising at least 50 contiguous nucleotides of the nucleotide sequence of SEQ ID NO:7.  
     
     
         6 . The nucleic acid molecule of  claim 5 , wherein the nucleic acid molecule comprises at least 100 contiguous nucleotides of the nucleotide sequence of SEQ ID NO:7.  
     
     
         7 . The nucleic acid molecule of  claim 5 , wherein the nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO:9.  
     
     
         8 . The nucleic acid molecule of  claim 5 , wherein the nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO:7.  
     
     
         9 . An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a fusion protein comprising amino acids 23-123 of SEQ ID NO:8.  
     
     
         10 . An isolated nucleic acid molecule that hybridizes to a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO:7 under conditions of incubation at 45° C. in 6.0×SSC followed by washing in 0.2×SSC/0.1% SDS at 65° C.  
     
     
         11 . The isolated nucleic acid molecule of  claim 1 , further comprising vector nucleic acid sequences.  
     
     
         12 . A host cell containing the nucleic acid molecule of  claim 1 .  
     
     
         13 . An isolated polypeptide comprising the amino acid sequence of SEQ ID NO:8.  
     
     
         14 . The isolated polypeptide of  claim 13 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:8.  
     
     
         15 . An isolated polypeptide comprising at least 25 contiguous amino acids of the amino acid sequence of SEQ ID NO:8.  
     
     
         16 . The isolated polypeptide of  claim 15 , wherein the polypeptide comprises at least 50 contiguous amino acids of the amino acid sequence of SEQ ID NO:8.  
     
     
         17 . A fusion protein comprising amino acids 23-123 of SEQ ID NO:8.  
     
     
         18 . An antibody which selectively binds to a polypeptide comprising the amino acid sequence of SEQ ID NO:8.  
     
     
         19 . A method for producing a polypeptide comprising the amino acid sequence of SEQ ID NO:8, the method comprising culturing the host cell of  claim 12  under conditions in which the polypeptide is expressed.  
     
     
         20 . A method for detecting the presence of a polypeptide in a sample, the method comprising: 
 (a) contacting the sample with a compound that selectively binds to a polypeptide comprising the amino acid sequence of SEQ ID NO:8; and    (b) determining whether the compound binds to a polypeptide in the sample.    
     
     
         21 . A kit comprising a compound that selectively binds to a polypeptide comprising the amino acid sequence of SEQ ID NO:8 and instructions for use.  
     
     
         22 . A method for identifying a compound that binds to a polypeptide, the method comprising the steps of: 
 (a) contacting a cell or a sample comprising a polypeptide comprising amino acids 23-123 of SEQ ID NO:8 with a test compound; and    (b) determining whether the polypeptide binds to the test compound.    
     
     
         23 . A method for identifying a compound that modulates the ability of a polypeptide to bind to Bcl-10, the method comprising: 
 (a) contacting a polypeptide comprising amino acids 23-123 of SEQ ID NO:8 with a test compound; and    (b) determining the effect of the test compound on the ability of the polypeptide to bind to Bcl-10.    
     
     
         24 . A method for identifying a compound that modulates the ability of a polypeptide to increase the activity of NF-kB, the method comprising: 
 (a) contacting a polypeptide comprising amino acids 23-123 of SEQ ID NO:8 with a test compound; and    (b) determining the effect of the test compound on the ability of the polypeptide to increase the activity of NF-kB.    
     
     
         25 . A method for detecting the presence of a nucleic acid molecule in a sample, the method comprising: 
 (a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to a nucleic acid molecule comprising SEQ ID NO:7 or SEQ ID NO:9; and    (b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample.    
     
     
         26 . A method for modulating the activity of a polypeptide, the method comprising contacting a polypeptide comprising the amino acid sequence of SEQ ID NO:8 or a cell expressing the polypeptide with a compound that binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.  
     
     
         27 . The method of  claim 26 , wherein the compound modulates the ability of the polypeptide to bind to Bcl-10.  
     
     
         28 . The method of  claim 26 , wherein the compound modulates the ability of the polypeptide to increase the activity of NF-kB.  
     
     
         29 . A method of treating a disorder associated with inappropriate apoptosis, the method comprising: 
 (a) selecting an individual that has a disorder associated with inappropriate apoptosis; and    (b) modulating the expression or activity of a polypeptide comprising the amino acid sequence of SEQ ID NO:8.    
     
     
         30 . A method of treating a disorder associated with inappropriate lymphocyte activation, the method comprising: 
 (a) selecting an individual that has a disorder associated with inappropriate lymphocyte activation; and    (b) modulating the expression or activity of a polypeptide comprising the amino acid sequence of SEQ ID NO:8.