Novel NPG-1 gene that is differentially expressed in prostate tumors

Abstract

The invention provides isolated nucleic acids molecules, designated NPG-1 nucleic acid molecules, which encode polypeptides involved in the modulation of a response in a tumor cell. The invention also provides antisense nucleic acid molecules, expression vectors containing NPG-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which an NPG-1 gene has been introduced or disrupted. The invention still further provides isolated NPG-1 polypeptides, fusion polypeptides, antigenic peptides, and anti-NPG-1 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

1 . An isolated nucleic acid molecule selected from the group consisting of: 
 a) a nucleic acid molecule comprising a nucleotide sequence which has at least 80% sequence identity to a nucleotide sequence of SEQ ID NO:1, or a complement thereof;    b) a nucleic acid molecule comprising a fragment of at least 1000 nucleotides of a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1, or a complement thereof;    c) a nucleic acid molecule which encodes a polypeptide comprising an amino acid sequence having at least about 76% sequence identity to the amino acid sequence of SEQ ID NO:2;    d) 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 acid residues of the amino acid sequence of SEQ ID NO:2; and    e) 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 comprising SEQ ID NO:1 under stringent conditions:    
     
     
         2 . The isolated nucleic acid molecule of  claim 1  which is selected from the group consisting of: 
 a) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, or a complement thereof; and  
 b) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2.  
 
     
     
         3 . The nucleic acid molecule of  claim 1  further comprising vector nucleic acid sequences.  
     
     
         4 . The nucleic acid molecule of  claim 1  further comprising nucleic acid sequences encoding a heterologous polypeptide.  
     
     
         5 . A host cell which contains the nucleic acid molecule of  claim 1 .  
     
     
         6 . The host cell of  claim 5  which is a mammalian host cell.  
     
     
         7 . A non-human mammalian host cell containing the nucleic acid molecule of  claim 1 .  
     
     
         8 . 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, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1 under stringent conditions;    c) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 80% homologous to a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1; and    d) a polypeptide comprising an amino acid sequence which has at least 76% sequence identity to the amino acid sequence of SEQ ID NO:2.    
     
     
         9 . The isolated polypeptide of  claim 8  comprising the amino acid sequence of SEQ ID NO:2.  
     
     
         10 . The polypeptide of  claim 8  further comprising heterologous amino acid sequences.  
     
     
         11 . An antibody which selectively binds to a polypeptide of  claim 8 .  
     
     
         12 . A method for producing a polypeptide selected from the group consisting of: 
 a) a polypeptide comprising the amino acid sequence of SEQ ID NO:2;    b) 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 naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1 under stringent conditions; comprising culturing the host cell of  claim 5  under conditions in which the nucleic acid molecule is expressed.    
     
     
         13 . A method for detecting the presence of a polypeptide of  claim 8  in a sample comprising: 
 a) contacting the sample with a compound which selectively binds to the polypeptide; and  
 b) determining whether the compound binds to the polypeptide in the sample to thereby detect the presence of a polypeptide of  claim 8  in the sample.  
 
     
     
         14 . The method of  claim 13 , wherein the compound which binds to the polypeptide is an antibody.  
     
     
         15 . A kit comprising a compound which selectively binds to a polypeptide of  claim 8  and instructions for use.  
     
     
         16 . A method for detecting the presence of a nucleic acid molecule in  claim 1  in a sample comprising: 
 a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule; and  
 b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample to thereby detect the presence of a nucleic acid molecule of  claim 1  in the sample.  
 
     
     
         17 . The method of  claim 16 , wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe.  
     
     
         18 . A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of  claim 1  and instructions for use.  
     
     
         19 . A method for identifying a compound which binds to a polypeptide of  claim 8  comprising: 
 a) contacting the polypeptide, or a cell expressing the polypeptide with a test compound; and  
 b) determining whether the polypeptide binds to the test compound.  
 
     
     
         20 . The method of  claim 19 , 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 detection of test compound/polypeptide binding;    b) detection of binding using a competition binding assay; and    c) detection of binding using an assay for an NPG-1 activity.    
     
     
         21 . A method of modulating the activity of a polypeptide of  claim 8  comprising contacting the polypeptide or a cell expressing the polypeptide with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.  
     
     
         22 . A method for identifying a compound which modulates the activity of a polypeptide of  claim 8  comprising: 
 a) contacting a polypeptide of  claim 8  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.  
 
     
     
         23 . A method of treating a subject having a disorder characterized by aberrant NPG-1 protein activity or nucleic acid expression, comprising administering to the subject an NPG-1 modulator such that the treatment of the subject occurs.  
     
     
         24 . The method of  claim 23 , wherein the disorder is selected from the group consisting of proliferative disorder and a neurological disorder.  
     
     
         25 . A method of determining if a subject mammal is at risk for a disorder related to, a lesion in an NPG-1 gene or the misexpression of an NPG-1 gene, comprising detecting, in a tissue of the subject, the presence or absence of a mutation of an NPG-1 gene.  
     
     
         26 . A method of determining if a subject mammal is at risk for a disorder related to an NPG-1 gene, comprising detecting, in a tissue of the subject, a non-wild type level of an NPG-1 RNA or polypeptide.