Tumor suppressor gene p33ing2

Abstract

The invention provides isolated nucleic acid and amino acid sequences of novel human tumor suppressors, antibodies to such tumor suppressors, methods of detecting such nucleic acids and proteins, methods of screening for modulators of tumor suppressors, and methods of diagnosing and treating tumors with such nucleic acids and proteins.

1 . A method for identifying a compound that modulates a tumor suppressor polypeptide p33ING2, the method comprising the steps of:
 (i) contacting the compound with a eukaryotic host cell or cell membrane in which has been expressed a tumor suppressor polypeptide p33ING2, wherein the polypeptide has greater than 70% amino acid sequence identity to a polypeptide comprising an amino acid sequence of SEQ ID NO:1; and   (ii) determining the functional effect of the compound upon the cell or cell membrane expressing the polypeptide.   
     
     
         2 . The method of  claim 1 , wherein the cell has the missense p33ING2 sequence of a polypeptide comprising an amino acid sequence of SEQ ID NO:6. 
     
     
         3 . A method of inhibiting cellular proliferation, the method comprising:
 transducing a cell with an expression vector, the vector comprising a nucleic acid encoding a tumor suppressor polypeptide p33ING2, wherein the polypeptide has greater than 70% amino acid sequence identity to a polypeptide comprising an amino acid sequence of SEQ ID NO:1.   
     
     
         4 . The method of  claim 3 , wherein the nucleic acid encodes a polypeptide comprising an amino acid sequence of SEQ ID NO:1. 
     
     
         5 . The method of  claim 3 , wherein the nucleic acid encodes a polypeptide having a molecular weight of about 28 kDa to about 38 kDa. cancer cell. 
     
     
         6 . The method of  claim 3 , wherein the cell has a missense or null endogenous p33ING2 phenotype. 
     
     
         7 . The method of  claim 3 , wherein the cell has a missense p33ING2 sequence of a polypeptide comprising an amino acid sequence of SEQ ID NO:6. 
     
     
         8 . A method of detecting the presence or absence of p33ING2 in mammalian tissue, the method comprising the steps of:
 (i) isolating a biological sample;   (ii) contacting the biological sample with a p33ING2-specific reagent that selectively associates with p33ING2; and   (iii) detecting the level of p33ING2-specific reagent that selectively associates with the sample.   
     
     
         9 . The method of  claim 8 , wherein the p33ING2-specific reagent is selected from the group consisting of a p33ING2-specific antibody, a p33ING2-specific primer, and a p33ING2-specific nucleic acid probe. 
     
     
         10 . The method of  claim 9 , wherein the p33ING2-specific nucleic acid probe binds to a nucleic acid comprising a nucleotide sequence of SEQ ID NO:7, or to a nucleic acid comprising a nucleotide sequence of SEQ ID NO:2, or to a nucleic acid comprising a nucleotide sequence of SEQ ID NO:10. 
     
     
         11 . The method of  claim 8 , wherein the biological sample comprises intact chromosome 4q35. 
     
     
         12 . The method of  claim 8 , wherein the p33ING2-specific reagent detects nucleic acid. 
     
     
         13 . The method of  claim 12 , wherein the nucleic acid is RNA. 
     
     
         14 . The method of  claim 8 , wherein the p33ING2-specific reagent is an antibody that selectively binds to p33ING2. 
     
     
         15 . The method of  claim 14 , wherein the antibody selectively binds to a p33ING2 polypeptide comprising an amino acid sequence of SEQ ID NO:1, but not to a p33ING1 polypeptide comprising an amino acid sequence of SEQ ID NO:8. 
     
     
         16 . The method of  claim 14 , wherein the antibody selectively binds to a p33ING2 polypeptide comprising an amino acid sequence of SEQ ID NO:5, but does not bind to a p33ING1 polypeptide comprising an amino acid sequence of SEQ ID NO:8. 
     
     
         17 . The method of  claim 8 , further comprising
 (iv) comparing an amount of p33ING2 detected in step (iii) to a control.   
     
     
         18 . A method of detecting the presence or absence of p33ING1 in mammalian tissue the method comprising the steps of:
 (i) isolating a biological sample;   (ii) contacting the biological sample with a p33ING1-specific antibody that selectively binds to p33ING1 but not to p33ING2; and   (iii) detecting the level of p33ING1-specific antibody that selectively associates with the sample.   
     
     
         19 . The method of  claim 19 , further comprising
 (iv) comparing an amount of p33ING1 detected in step (iii) to a control.