Growth arrest homeobox gene

Abstract

A novel growth arrest homeobox gene has been discovered and the nucleotide sequences have been determined in both the rat and the human. The expression of the novel homeobox gene inhibits vascular smooth muscle cell growth. The growth arrest homeobox gene hereinafter referred to as the “Gax gene” and its corresponding proteins are useful in the study of vascular smooth muscle cell proliferation and in the treatment of blood vessel diseases that result from excessive smooth muscle cell proliferation, particularly after balloon angioplasty.

What is claimed is:  
     
         1 . A DNA sequence encoding a protein or portion thereof, which inhibits vascular smooth muscle cell proliferation.  
     
     
         2 . The DNA sequence of  claim 1 , comprising the nucleotide sequence substantially as shown in FIG. 1.  
     
     
         3 . The DNA sequence of  claim 1 , comprising the nucleotide sequence substantially as shown in FIG. 3.  
     
     
         4 . The DNA sequence of  claim 1 , comprising the nucleotide sequence from about 200 to about 1108 substantially as shown in FIG. 1.  
     
     
         5 . The DNA sequence of  claim 1 , comprising the nucleotide sequence from about 749 to about 919 substantially as shown in FIG. 1.  
     
     
         6 . The messenger RNA transcript of the DNA of  claim 1 .  
     
     
         7 . An isolated protein which inhibits vascular smooth muscle cell growth.  
     
     
         8 . The protein of  claim 7  having a molecular weight of from about 30 kDA to about 36 kDa.  
     
     
         9 . The protein of  claim 7 , comprising the amino acid sequence substantially as shown in FIG. 1.  
     
     
         10 . The protein of  claim 7 , comprising the amino acid sequence substantially as shown in FIG. 3.  
     
     
         11 . The protein of  claim 7 , comprising the amino acid sequence from about 1 to about 303 substantially as shown in FIG. 1.  
     
     
         12 . The protein of  claim 7 , further comprising glutathione S-transferase.  
     
     
         13 . A vector containing the DNA sequence of  claim 1 .  
     
     
         14 . The vector of  claim 13 , wherein the nucleotide sequence is the nucleotide sequence of  claim 2 .  
     
     
         15 . The vector of  claim 13 , wherein the nucleotide sequence is the nucleotide sequence of  claim 3 .  
     
     
         16 . The vector of  claim 13 , wherein the nucleotide sequence is the nucleotide sequence of  claim 4 .  
     
     
         17 . The vector of  claim 13 , wherein the nucleotide sequence is the nucleotide sequence of  claim 5 .  
     
     
         18 . A host cell transformed by vector of  claim 13  containing the nucleotide sequence coding for Gax protein.  
     
     
         19 . A host cell transformed by vector of  claim 14  containing the nucleotide sequence coding for Gax protein.  
     
     
         20 . A host cell transformed by vector of  claim 15  containing the nucleotide sequence coding for Gax protein.  
     
     
         21 . A host cell transformed by vector of  claim 16  containing the nucleotide sequence encoding the Gax protein.  
     
     
         22 . A host cell transformed by vector of  claim 17  containing the nucleotide sequence encoding the Gax protein.  
     
     
         23 . A process for the preparation of Gax protein comprising culturing the transformed host of  claim 18  under conditions suitable for the expression of Gax protein and recovering the Gax protein.  
     
     
         24 . A process for the preparation of a protein which inhibits the proliferation of vascular smooth muscle cells comprising culturing the transformed host of  claim 19  under conditions suitable for the expression of the protein and recovering the protein.  
     
     
         25 . A process for the preparation of a protein which inhibits the proliferation of vascular smooth muscle cells comprising culturing the transformed host of  claim 20  under conditions suitable for the expression of the protein and recovering the protein.  
     
     
         26 . A process for the preparation of a protein which inhibits the proliferation of vascular smooth muscle cells comprising culturing the transformed host of  claim 21  under conditions suitable for the expression of the protein and recovering the protein.  
     
     
         27 . The Gax protein made by the process selected from the processes of  claim 23 ,  claim 24 ,  claim 25 , and  claim 26 .  
     
     
         28 . A method for inhibiting the proliferation of eukaryotic cells, comprising the following steps: 
 a. providing nucleic acid sequence encoding a protein, or portion thereof, which inhibits vascular smooth muscle cell proliferation; and    b. administering said nucleic acid or said protein to the cells.    
     
     
         29 . The method of  claim 28  wherein the nucleic acid is DNA.  
     
     
         30 . The method of  claim 28  wherein the nucleic acid is RNA.  
     
     
         31 . The method of  claim 28  wherein the protein comprises the amino acid sequence from about 1 to 303 shown in FIG. 1.  
     
     
         32 . The method of  claim 28  wherein the cells are vascular smooth muscle cells.