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

Abstract

Novel CARD-12 polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated CARD-12 proteins, the invention further provides CARD-12, fusion proteins, antigenic peptides and anti-CARD-12 antibodies. The invention also provides CARD-12 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-12 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 at least 50 contiguous nucleotides of SEQ ID NO:1.  
     
     
         2 . The isolated nucleic acid molecule of  claim 1  wherein the nucleic molecule comprises at least 150 contiguous nucleotide of SEQ ID NO:1.  
     
     
         3 . The isolated nucleic acid molecule of  claim 1  wherein the nucleic acid molecule comprises at least 500 contiguous nucleotide of SEQ ID NO:1.  
     
     
         4 . An isolated nucleic acid molecule comprising at least 50 contiguous nucleotides of SEQ ID NO:3.  
     
     
         5 . The isolated nucleic acid molecule of  claim 4  wherein the nucleic acid molecule comprises at least 150 contiguous nucleotide of SEQ ID NO:3.  
     
     
         6 . The isolated nucleic acid molecule of  claim 4  wherein the nucleic acid molecule comprises at least 500 contiguous nucleotide of SEQ ID NO:3.  
     
     
         7 . The isolated nucleic acid molecule of  claim 1  wherein the nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO:1.  
     
     
         8 . The isolated nucleic acid molecule of  claim 1  wherein the nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO:3.  
     
     
         9 . An isolated nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising at least 25 contiguous amino acids of SEQ ID NO:2.  
     
     
         10 . The isolated nucleic acid molecule of  claim 9  wherein the polypeptide comprises at least 150 contiguous amino acids of SEQ ID NO:2.  
     
     
         11 . The isolated nucleic acid molecule of  claim 9  wherein the polypeptide comprises at least one domain selected from the group consisting of a CARD domain, a NACHT domain, a leucine rich repeat domain, and an NBS domain.  
     
     
         12 . The isolated nucleic acid molecule of  claim 9  wherein the polypeptide comprises at least two domains selected from the group consisting of a CARD domain, a NACHT motif domain, a leucine rich repeat domain, and an NBS domain.  
     
     
         13 . The isolated nucleic acid molecule of  claim 9  wherein the polypeptide comprises at least two NACHT motif domains.  
     
     
         14 . The isolated nucleic acid molecule of  claim 9  wherein the polypeptide comprises at least two leucine rich repeat domains.  
     
     
         15 . The isolated nucleic acid molecule of  claim 9  wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:2.  
     
     
         16 . An isolated nucleic acid molecule that hybridizes to a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO:3 under conditions of incubation at 45° C. in 6.0× SSC followed by washing in 0.2× SSC/0.1% SDS at 65° C.  
     
     
         17 . The nucleic acid molecule of  claim 1  further comprising vector nucleic acid sequences.  
     
     
         18 . The nucleic acid molecule of  claim 17  wherein the vector nucleic acid sequences comprise expression control sequences.  
     
     
         19 . A host cell that contains the nucleic acid molecule of  claim 1 .  
     
     
         20 . The host cell of  claim 19  wherein the host cell is a mammalian cell.  
     
     
         21 . An isolated polypeptide comprising at least 15 contiguous amino acids of SEQ ID NO:2.  
     
     
         22 . The isolated polypeptide of  claim 21  wherein the polypeptide comprises at least 75 contiguous amino acids of SEQ ID NO:2.  
     
     
         23 . The isolated polypeptide of  claim 21  comprising the amino acid sequence of SEQ ID NO:2.  
     
     
         24 . An isolated polypeptide comprising the amino acid sequence of SEQ ID NO:2 wherein up to 10 amino acids are replaced by conservative substitutions.  
     
     
         25 . A fusion protein comprising at least 25 contiguous amino acids of SEQ ID NO:2  
     
     
         26 . An antibody which selectively binds to a polypeptide consisting of the amino acid sequence of SEQ IN NO:2.  
     
     
         27 . A method for detecting the presence of a polypeptide of  claim 21  in a sample, comprising: 
 a) contacting the sample with a compound which selectively binds to a polypeptide of  claim 2;  and  
 b) determining whether the compound binds to the polypeptide in the sample.  
 
     
     
         28 . The method of  claim 27 , wherein the compound that binds to the polypeptide is an antibody.  
     
     
         29 . A kit comprising a compound that selectively binds to a polypeptide of  claim 22  and instructions for use.  
     
     
         30 . A method for detecting the presence of a nucleic acid molecule of  claim 1  in a sample, comprising the steps of: 
 a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule of  claim 1;  and  
 b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample.  
 
     
     
         31 . The method of  claim 30 , wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe.  
     
     
         32 . A kit comprising a compound that selectively hybridizes to a nucleic acid molecule of  claim 1  and instructions for use.  
     
     
         33 . A method for identifying a compound which binds to a polypeptide of comprising the amino acid sequence of SEQ ID NO:2 the method comprising the steps of: 
 a) contacting a polypeptide, or a cell expressing a polypeptide comprising the amino acid sequence of SEQ ID NO:2 with a test compound; and    b) determining whether the polypeptide binds to the test compound.    
     
     
         34 . The method of  claim 33 , wherein the binding of the test compound to the polypeptide is detected by a method selected from the group consisting of: 
 a) detection of binding by direct detecting of test compound/polypeptide binding;    b) detection of binding using a competition binding assay;    c) detection of binding using an assay for CARD-12-mediated signal transduction; and    d) detection of binding of a CARD-12 to a CARD domain.    
     
     
         35 . A method for identifying a compound that modulates the activity of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, comprising: 
 a) contacting a polypeptide of  claim 21  with a test compound; and    b) determining the effect of the test compound on the activity of the polypeptide to thereby identify a compound which modulates the activity of the polypeptide.