Nucleic acid molecules encoding DRT111 and uses thereof

Abstract

Novel DRT111 polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to an isolated, full-length DRT111 protein, the invention further provides isolated DRT111 fusion proteins, antigenic peptides and anti-DRT111 antibodies. The invention also provides DRT111 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 DRT111 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 selected from the group consisting of: 
 (a) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID No:2;    (b) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2; and    (c) a nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, the complement of SEQ ID NO:1, or the complement of SEQ ID NO:3 under stringent conditions.    
     
     
         2 . An isolated nucleic acid molecule selected from the group consisting of: 
 (a) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3;    (b) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3, wherein the “T”s are replaced with “U”s;    (c) a nucleic acid molecule which is complementary to (a) and (b); and    (d) fragments of (a), (b) or (c) that comprise at least 30 contiguous nucleotides of SEQ ID NO:1, SEQ ID NO:3, the complement of SEQ ID NO:1, or the complement of SEQ ID NO:3.    
     
     
         3 . An isolated nucleic acid molecule selected from the group consisting of: 
 (a) a nucleic acid molecule comprising a nucleotide sequence which is at least 55% identical to the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3, or a complement thereof;    (b) a nucleic acid molecule comprising a nucleotide sequence that hybridizes to a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3 under stringent conditions, or a complement thereof; and    (c) a nucleic acid molecule comprising a nucleotide sequence that hybridizes to a nucleic acid molecule consisting of the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Accession Number ______ under stringent conditions, or a complement thereof.    
     
     
         4 . An isolated polypeptide selected from the group consisting of: 
 (a) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2;    (b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2 or an amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Accession Number ______, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to the complement of a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3 under stringent conditions; and    (c) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 55% identical to a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3.    
     
     
         5 . An isolated polypeptide comprising the amino acid sequence of SEQ ID NO:2 or an amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Accession Number ______.  
     
     
         6 . A method of determining whether a cell has a drug-resistant phenotype, the method comprising: 
 (a) measuring the expression of DRT111 in the cell; and    (b) comparing the expression of DRT111 measured in step (a) to the expression of DRT111 in a control cell not having a drug-resistant phenotype;    whereby increased expression of DRT111 in the cell compared to the control cell indicates that the cell has a drug-resistant phenotype.    
     
     
         7 . A method for modulating the drug resistance of a cell, the method comprising modulating DRT111 expression within the cell.  
     
     
         8 . A method of reducing the drug resistance of a cell, the method comprising contacting the cell with a molecule which reduces expression of DRT111 within the cell.  
     
     
         9 . A method of improving the effectiveness of a drug in a mammal having a disorder associated with the presence of drug-resistant neoplastic cells, the method comprising the steps of: 
 (a) administering a chemotherapeutic drug to said mammal; and    (b) co-administering a molecule which reduces expression of DRT111 to said mammal.    
     
     
         10 . A method of identifying a compound that modulates the drug resistance of a cell, the method comprising: 
 (a) contacting the cell with a test compound;    (b) measuring expression of DRT111 in the cell;    (c) comparing the expression of DRT111 measured in step (b) to expression of DRT111 in a control cell not contacted with the test compound; and    (d) identifying the test compound as a modulator of drug resistance when the level of DRT111 expression in the cell contacted with the test compound differs from the level of DRT111 expression in control cell not contacted with the test compound.    
     
     
         11 . A method of treating a mammal suspected of having a disorder associated with the presence of drug-resistant cells, the method comprising administering to the mammal a compound that reduces the expression of DRT111, said reduction being sufficient to modulate the drug resistance of the cells associated with the disorder.  
     
     
         12 . A method for treating a patient who has a neoplastic disorder, the method comprising administering to the patient a therapeutically effective amount of a compound that decreases the expression of DRT111.  
     
     
         13 . A method for increasing drug resistance in a cell that has an undesirably low level of DRT111 expression, the method comprising administering to the cell a compound that increases the expression of DRT111 in the cell.