Human c-Maf compositions and methods of use thereof

Abstract

Isolated nucleic acid molecules encoding human c-Maf, and isolated c-Maf proteins, are provided. The invention further provides antisense 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 carrying a human c-Maf transgene. The invention further provides human c-Maf fusion proteins and anti-human c-Maf antibodies. Methods of using the human c-maf compositions of the invention are also disclosed, including methods for detecting human c-Maf activity in a biological sample, methods of modulating human c-Maf activity in a cell, and methods for identifying agents that modulate the activity of human c-Maf.

We claim:  
     
         1 . An isolated nucleic acid molecule comprising a nucleotide sequence encoding human c-Maf.  
     
     
         2 . The nucleic acid molecule of  claim 1 , which comprises the nucleotide sequence of the coding region of the NheI/XbaI insert of plasmid pHu-c-Maf (ATCC Accession No. 98671).  
     
     
         3 . The nucleic acid molecule of  claim 1 , which comprises the nucleotide sequence of SEQ ID NO: 1.  
     
     
         4 . The nucleic acid molecule of  claim 1 , which has at least 98% nucleotide identity with the nucleotide sequence of SEQ ID NO: 1.  
     
     
         5 . The nucleic acid molecule of  claim 1 , which has at least 99% nucleotide identity with the nucleotide sequence of SEQ ID NO: 1.  
     
     
         6 . The nucleic acid molecule of  claim 1 , which has at least 99.5% nucleotide identity with the nucleotide sequence of SEQ ID NO: 1.  
     
     
         7 . An isolated nucleic acid molecule comprising the nucleotide sequence of the coding region of the NheI/XbaI insert of plasmid pHu-c-Maf (ATCC Accession No. 98671).  
     
     
         8 . An isolated nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 1.  
     
     
         9 . A vector comprising the nucleic acid molecule of  claim 1 .  
     
     
         10 . The vector of  claim 9 , which is an expression vector.  
     
     
         11 . A host cell containing the vector of  claim 10 .  
     
     
         12 . A method for producing a human c-Maf protein comprising culturing the host cell of  claim 11  in a suitable medium until a human c-Maf protein is produced.  
     
     
         13 . The method of  claim 12 , further comprising isolating the human c-Maf protein from the medium or the host cell.  
     
     
         14 . An isolated human c-Maf protein.  
     
     
         15 . The protein of  claim 14 , which comprises the amino acid sequence encoded by the coding region of the NheI/XbaI insert of plasmid pHu-c-Maf (ATCC Accession No. 98671).  
     
     
         16 . The protein of  claim 14 , which comprises the amino acid sequence of SEQ ID NO: 2.  
     
     
         17 . The protein of  claim 14 , which has at least 98% amino acid identity with the amino acid sequence of SEQ ID NO: 2.  
     
     
         18 . The protein of  claim 14 , which has at least 99% amino acid identity with the amino acid sequence of SEQ ID NO: 2.  
     
     
         19 . The protein of  claim 14 , which has at least 99.5% amino acid identity with the amino acid sequence of SEQ ID NO: 2.  
     
     
         20 . An isolated protein comprising the amino acid sequence of SEQ ID NO: 2.  
     
     
         21 . A fusion protein comprising a human c-Maf protein operatively linked to a polypeptide other than human c-Maf.  
     
     
         22 . Antibodies that specifically bind human c-Maf protein.  
     
     
         23 . The antibodies of  claim 22 , which are polyclonal antibodies.  
     
     
         24 . The antibodies of  claim 22 , which are monoclonal antibodies.  
     
     
         25 . The antibodies of  claim 22 , which are coupled to a detectable substance.  
     
     
         26 . A nonhuman transgenic animal that contains cells carrying a transgene encoding a human c-Maf protein.  
     
     
         27 . A method for detecting the presence of human c-Maf in a biological sample comprising contacting the biological sample with an agent capable of detecting an indicator of human c-Maf activity such that the presence of human c-Maf is detected in the biological sample.  
     
     
         28 . A method for modulating human c-Maf activity in a cell comprising contacting the cell with an agent that modulates human c-Maf activity such that human c-Maf activity in the cell is modulated.  
     
     
         29 . A method for identifying a compound that modulates the activity of a human c-Maf protein, comprising 
 providing an indicator composition that comprises a human c-Maf protein;    contacting the indicator composition with a test compound; and    determining the effect of the test compound on the activity of the human c-Maf protein in the indicator composition to thereby identify a compound that modulates the activity of a human c-Maf protein.    
     
     
         30 . The method of  claim 29 , wherein: 
 the indicator composition comprises a human c-Maf protein and a DNA molecule to which the human c-Maf protein binds; and    the effect of the test compound on the activity of the human c-Maf protein is determined by evaluating the binding of the human c-Maf protein to the DNA molecule in the presence and absence of the test compound.    
     
     
         31 . The method of  claim 29 , wherein: 
 the indicator composition is a cell comprising a human c-Maf protein and a reporter gene responsive to the human c-Maf protein; and    the effect of the test compound on the activity of the human c-Maf protein is determined by evaluating the expression of the reporter gene in the presence and absence of the test compound.    
     
     
         32 . The method of  claim 29 , further comprising determining the effect of the test compound on an immune response to thereby identify a compound that modulates an immune response.