33167, a novel human hydrolase and uses therefor

Abstract

The invention provides isolated nucleic acids molecules, designated HYDL-1 nucleic acid molecules, which encode novel hydrolase molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing HYDL-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which an HYDL-1 gene has been introduced or disrupted. The invention still further provides isolated HYDL-1 proteins, fusion proteins, antigenic peptides and anti-HYDL-1 antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

What is claimed:  
     
         1 . An isolated nucleic acid molecule selected from the group consisting of: 
 (a) a nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:1; and    (b) a nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:3.    
     
     
         2 . An isolated nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2.  
     
     
         3 . An isolated nucleic acid molecule comprising the nucleotide sequence contained in the plasmid deposited with ATCC® as Accession Number ______.  
     
     
         4 . An isolated nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2.  
     
     
         5 . 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 3, or a complement thereof;    b) a nucleic acid molecule comprising a fragment of at least 50 nucleotides of a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1 or 3, or a complement thereof,    c) a nucleic acid molecule which encodes a polypeptide comprising an amino acid sequence at least about 60% identical to the amino acid sequence of SEQ ID NO:2; and    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.    
     
     
         6 . An isolated nucleic acid molecule which hybridizes to the nucleic acid molecule of any one of  claim 1 ,  2 ,  3 ,  4 , or  5  under stringent conditions.  
     
     
         7 . An isolated nucleic acid molecule comprising a nucleotide sequence which is complementary to the nucleotide sequence of the nucleic acid molecule of any one of  claim 1 ,  2 ,  3 ,  4 , or  5 .  
     
     
         8 . An isolated nucleic acid molecule comprising the nucleic acid molecule of any one of  claim 1 ,  2 ,  3 ,  4 , or  5 , and a nucleotide sequence encoding a heterologous polypeptide.  
     
     
         9 . A vector comprising the nucleic acid molecule of any one of  claim 1 ,  2 ,  3 ,  4 , or  5 .  
     
     
         10 . The vector of  claim 9 , which is an expression vector.  
     
     
         11 . A host cell transfected with the expression vector of  claim 10 .  
     
     
         12 . A method of producing a polypeptide comprising culturing the host cell of  claim 11  in an appropriate culture medium to, thereby, produce the polypeptide.  
     
     
         13 . 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 consisting of SEQ ID NO:1 or 3 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 or 3;    d) a polypeptide comprising an amino acid sequence which is at least 60% identical to the amino acid sequence of SEQ ID NO:2.    
     
     
         14 . The isolated polypeptide of  claim 13  comprising the amino acid sequence of SEQ ID NO:2.  
     
     
         15 . The polypeptide of  claim 13 , further comprising heterologous amino acid sequences.  
     
     
         16 . An antibody which selectively binds to a polypeptide of  claim 13 .  
     
     
         17 . A method for detecting the presence of a polypeptide of  claim 13  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 13  in the sample.  
 
     
     
         18 . The method of  claim 17 , wherein the compound which binds to the polypeptide is an antibody.  
     
     
         19 . A kit comprising a compound which selectively binds to a polypeptide of  claim 13  and instructions for use.  
     
     
         20 . A method for detecting the presence of a nucleic acid molecule of any one of  claim 1 ,  2 ,  3 ,  4 , or  5  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 any one of  claim 1 ,  2 ,  3 ,  4 , or  5  in the sample.  
 
     
     
         21 . The method of  claim 20 , wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe.  
     
     
         22 . A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of any one of  claim 1 ,  2 ,  3 ,  4 , or  5  and instructions for use.  
     
     
         23 . A method for identifying a compound which binds to a polypeptide of  claim 13  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.  
 
     
     
         24 . The method of  claim 23 , 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 HYDL-1 activity.    
     
     
         25 . A method for modulating the activity of a polypeptide of  claim 13  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.  
     
     
         26 . A method for identifying a compound which modulates the activity of a polypeptide of  claim 13  comprising: 
 a) contacting a polypeptide of  claim 13  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.  
 
     
     
         27 . A method of identifying a nucleic acid molecule associated with a cellular proliferative disorder comprising: 
 a) contacting a sample comprising nucleic acid molecules with a hybridization probe comprising at least 25 contiguous nucleotides of SEQ ID NO:1 or 3; and    b) detecting the presence of a nucleic acid molecule in said sample that hybridizes to said probe, thereby identifying a nucleic acid molecule associated with a cellular proliferative disorder.    
     
     
         28 . A method of identifying a subject having a cellular proliferative disorder, or at risk for developing a cellular proliferative disorder comprising: 
 a) contacting a sample obtained from said subject comprising nucleic acid molecules with a hybridization probe comprising at least 25 contiguous nucleotides of SEQ ID NO:1 or 3; and    b) detecting the presence of a nucleic acid molecule in said sample that hybridizes to said probe, thereby identifying a subject having a cellular proliferative disorder, or at risk for developing a cellular proliferative disorder.    
     
     
         29 . The method of either of  claim 27  or  28 , wherein said hybridization probe is detectably labeled.  
     
     
         30 . The method of either of  claim 27  or  28 , wherein said sample comprising nucleic acid molecules is subjected to agarose gel electrophoresis and southern blotting prior to contacting with said hybridization probe.  
     
     
         31 . The method of either of  claim 27  or  28 , wherein said sample comprising nucleic acid molecules is subjected to agarose gel electrophoresis and northern blotting prior to contacting with said hybridization probe.  
     
     
         32 . The method of either of  claim 27  or  28 , wherein said detecting is by in situ hybridization.  
     
     
         33 . A method of identifying a nucleic acid associated with a cellular proliferative disorder comprising: 
 a) contacting a sample comprising nucleic acid molecules with a first and a second amplification primer, said first primer comprising at least 25 contiguous nucleotides of SEQ ID NO:1 or 3 and said second primer comprising at least 25 contiguous nucleotides from the complement of SEQ ID NO:1 or 3;    b) incubating said sample under conditions that allow nucleic acid amplification; and    c) detecting the presence of a nucleic acid molecule in said sample that is amplified, thereby identifying a nucleic acid molecule associated with a cellular proliferative disorder.    
     
     
         34 . A method of identifying a subject having a cellular proliferative disorder, or at risk for developing a cellular proliferative disorder comprising: 
 a) contacting a sample obtained from said subject comprising nucleic acid molecules with a first and a second amplification primer, said first primer comprising at least 25 contiguous nucleotides of SEQ ID NO:1 or 3 and said second primer comprising at least 25 contiguous nucleotides from the complement of SEQ ID NO:1 or 3;    b) incubating said sample under conditions that allow nucleic acid amplification; and    c) detecting the presence of a nucleic acid molecule in said sample that is amplified, thereby identifying a subject having a cellular proliferative disorder, or at risk for developing a cellular proliferative disorder.    
     
     
         35 . The method of either of  claim 33  or  34 , wherein said sample comprising nucleic acid molecules is subjected to agarose gel electrophoresis after said incubation step.  
     
     
         36 . The method of any one of  claim 27 ,  28 ,  33  or  34 , wherein said method is used to detect mRNA in said sample.  
     
     
         37 . The method of any one of  claim 27 ,  28 ,  33  or  34 , wherein said method is used to detect genomic DNA in said sample.  
     
     
         38 . A method of identifying a polypeptide associated with a cellular proliferative disorder comprising: 
 a) contacting a sample comprising polypeptides with an HYDL-1 binding substance; and    b) detecting the presence of a polypeptide in said sample that binds to said HYDL-1 binding substance, thereby identifying a polypeptide associated with a cellular proliferative disorder.    
     
     
         39 . A method of identifying a subject having a cellular proliferative disorder, or at risk for developing a cellular proliferative disorder comprising: 
 a) contacting a sample obtained from said subject comprising polypeptides with an HYDL-1 binding substance; and    b) detecting the presence of a polypeptide in said sample that binds to said HYDL-1 binding substance, thereby identifying a subject having a cellular proliferative disorder, or at risk for developing a cellular proliferative disorder.    
     
     
         40 . The method of either of  claim 38  or  39 , wherein said binding substance is an antibody.  
     
     
         41 . The method of either of  claim 38  or  39 , wherein said binding substance is detectably labeled.  
     
     
         42 . A method for identifying a compound capable of treating a cellular proliferative disorder characterized by aberrant HYDL-1 nucleic acid expression or HYDL-1 polypeptide activity comprising assaying the ability of the compound to modulate HYDL-1 nucleic acid expression or HYDL-1 polypeptide activity, thereby identifying a compound capable of treating a cellular proliferative disorder characterized by aberrant HYDL-1 nucleic acid expression or HYDL-1 polypeptide activity.  
     
     
         43 . The method of  claim 42 , wherein the ability of the compound to modulate the activity of the HYDL-1 polypeptide is determined by detecting modulation of cell progression through the cell cycle.  
     
     
         44 . A method for treating a subject having a cellular proliferative disorder characterized by aberrant HYDL-1 polypeptide activity or aberrant HYDL-1 nucleic acid expression comprising administering to the subject an HYDL-1 modulator, thereby treating said subject having a cellular proliferative disorder.  
     
     
         45 . The method of any one of  claim 27 ,  28 ,  33 ,  34 ,  38 ,  39 ,  42  or  44 , wherein the disorder is a cancer.  
     
     
         46 . The method of any one of  claim 27 ,  28 ,  33 ,  34 ,  38 ,  39 ,  42  or  44 , wherein the disorder is lung cancer.  
     
     
         47 . The method of  claim 44 , wherein the HYDL-1 modulator is a small molecule.  
     
     
         48 . The method of  claim 44 , wherein said HYDL-1 modulator is administered in a pharmaceutically acceptable formulation.  
     
     
         49 . The method of  claim 44 , wherein said HYDL-1 modulator is administered using a gene therapy vector.  
     
     
         50 . The method of  44 , wherein the HYDL-1 modulator is capable of modulating HYDL-1 polypeptide activity.  
     
     
         51 . The method of  claim 50 , wherein the HYDL-1 modulator is an anti-HYDL-1 antibody.  
     
     
         52 . The method of  claim 50 , wherein the HYDL-1 modulator is a HYDL-1 polypeptide comprising the amino acid sequence of SEQ ID NO:2, or a fragment thereof.  
     
     
         53 . The method of  claim 44 , wherein the HYDL-1 modulator is capable of modulating HYDL-1 nucleic acid expression.  
     
     
         54 . The method of  claim 53 , wherein the HYDL-1 modulator is an antisense HYDL-1 nucleic acid molecule .  
     
     
         55 . The method of  claim 53 , wherein the HYDL-1 modulator is a ribozyme.  
     
     
         56 . The method of  claim 53 , wherein the HYDL-1 modulator comprises the nucleotide sequence of SEQ ID NO:1 or 3, or a fragment thereof.  
     
     
         57 . A method for identifying a compound capable of modulating cell proliferation comprising: 
 a) contacting a cell with a test compound; and    b) assaying the ability of the test compound to modulate the expression of an HYDL-1 nucleic acid or the activity of an HYDL-1 polypeptide; thereby identifying a compound capable of modulating cell proliferation.    
     
     
         58 . A method for modulating cell proliferation comprising contacting a cell with an HYDL-1 modulator, thereby modulating cell proliferation.