32142,21481,25964,21686, Novel dehydrogenase molecules and uses therefor

Abstract

The invention provides isolated nucleic acids molecules, designated DHDR nucleic acid molecules, which encode novel DHDR-related dehydrogenase molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing DHDR nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a DHDR gene has been introduced or disrupted. The invention still further provides isolated DHDR proteins, fusion proteins, antigenic peptides and anti-DHDR antibodies. Diagnostic 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 is at least 60% identical to the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO:3, SEQ ID NO:7 or SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:12, or SEQ ID NO:14 or SEQ ID NO:16, or a complement thereof;   b) a nucleic acid molecule which encodes a polypeptide comprising an amino acid sequence which is at least 60% identical to the amino acid sequence of SEQ ID NO:2, SEQ ID NO:8, SEQ ID NO:11, or SEQ ID NO:15;   c) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:8, SEQ ID NO:11, or SEQ ID NO:15, wherein the fragment comprises at least 16 contiguous amino acids of SEQ ID NO:2, SEQ ID NO:8, SEQ ID NO:11, or SEQ ID NO:15; and   d) a nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:8, SEQ ID NO:11, or SEQ ID NO:15, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising SEQ ID NO: 1 or SEQ ID NO:3, SEQ ID NO:7 or SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:12, or SEQ ID NO:14 or SEQ ID NO:16, or a complement thereof, under stringent conditions.   
     
     
         2 . The isolated nucleic acid molecule of  claim 1 , further comprising a nucleotide sequence encoding a heterologous polypeptide. 
     
     
         3 . A vector comprising the nucleic acid molecule of  claim 1 . 
     
     
         4 . A host cell comprising the vector of  claim 3 . 
     
     
         5 . A method of producing a polypeptide comprising culturing the host cell of  claim 4  in an appropriate culture medium to thereby produce the polypeptide. 
     
     
         6 . 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, SEQ ID NO:8, SEQ ID NO:11, or SEQ ID NO:15, wherein the fragment comprises at least 16 contiguous amino acids of SEQ ID NO:2, SEQ ID NO:8, SEQ ID NO:11, or SQ ID NO:15;   b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:8, SEQ ID NO:11, or SEQ ID NO:15, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a complement of a nucleic acid molecule consisting of SEQ ID NO:1 or SEQ ID NO:3, SEQ ID NO:7 or SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:12, or SEQ ID NO:14 or SEQ ID NO:16 under stringent conditions;   c) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;   d) a polypeptide comprising an amino acid sequence which is at least 60% identical to the amino acid sequence of SEQ ID NO:2, SEQ ID NO:8, SEQ ID NO:11, or SEQ ID NO:15.   
     
     
         7 . The isolated polypeptide of  claim 6  comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:8, or SEQ ID NO:11. 
     
     
         8 . The polypeptide of  claim 6 , further comprising heterologous amino acid sequences. 
     
     
         9 . An antibody which selectively binds to a polypeptide of  claim 6 . 
     
     
         10 . A method for detecting the presence of a polypeptide of  claim 6  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 6  in the sample.   
     
     
         11 . The method of  claim 10 , wherein the compound which binds to the polypeptide is an antibody. 
     
     
         12 . A method for detecting the presence of a nucleic acid molecule of  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.   
     
     
         13 . The method of  claim 12 , wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe. 
     
     
         14 . A method for identifying a compound which binds to a polypeptide of  claim 6  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.   
     
     
         15 . The method of  claim 14 , 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 DHDR activity.   
     
     
         16 . A method for identifying a compound which modulates the activity of a polypeptide of  claim 6  comprising:
 a) contacting a polypeptide of  claim 6  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.   
     
     
         17 . The method of  claim 16 , wherein said activity is modulation of virus activity. 
     
     
         18 . A method for identifying a compound which modulates virus activity comprising:
 a) contacting the polypeptide of  claim 6 , or a cell expressing the polypeptide with a test compound; and   b) identifying the compound as a modulator of virus activity by determining the effect of the test compound on the activity of the polypeptide.   
     
     
         19 . The method of  claim 16 , wherein said activity is modulation of cellular proliferation. 
     
     
         20 . A method for identifying a compound which modulates cellular proliferation comprising:
 a) contacting the polypeptide of  claim 6 , or a cell expressing the polypeptide with a test compound; and   b) identifying the compound as a modulator of cellular proliferation by determining the effect of the test compound on the activity of the polypeptide.