Proteins suppressing proliferation of lympho-hematopoietic cells

Abstract

A novel protein having the activity to suppress proliferation of lympho-hematopoietic cells derived from BNS2.4 cells, its gene, a method for preparing them and their uses are provided. The novel protein has been identified from a stromal cell line BMS2.4 by expression cloning targeting mouse myelomonocytic leukemia cell line WEHI3. This protein and its gene are useful for treating lympho-hematopoietic disorders.

What is claimed is:  
     
         1 . A protein that suppresses the proliferation of lympho-hematopoietic cells selected from the group consisting of: 
 (a) a protein comprising the amino acid sequence as set forth in SEQ ID NO: 3;    (b) a protein comprising a derivative of the amino acid sequence set forth in SEQ ID NO: 3, in which one or more amino acids are substituted, deleted, inserted, and/or added; and    (c) a protein encoded by a DNA hybridizing with the DNA comprising the nucleotide sequence as set forth in SEQ ID NO: 1.    
     
     
         2 . The protein according to  claim 1 , wherein the lympho-hematopoietic cells are selected from the group consisting of B lineage cell line, 1 A9, BC7.12, BC7.7, F10, 2E8, 18-81, 7OZ/3, WEHI231 and SP2/0, T lineage lymphoma cell line BW1597, and myelomonocytic leukemia cell line WEHI3.  
     
     
         3 . A DNA encoding the protein according to  claim 1 .  
     
     
         4 . The DNA of  claim 3 , comprising the coding region of the nucleotide sequence as set forth in SEQ ID NO: 1.  
     
     
         5 . A vector comprising the DNA of  claim 3 .  
     
     
         6 . A host cell retaining the vector of  claim 5 .  
     
     
         7 . A method for preparing the protein of  claim 1 , the method comprising culturing the host cell of  claim 6  and recovering recombinant proteins expressed in the cell from the cultured cell or culture supernatant thereof.  
     
     
         8 . An antibody to the protein according to  claim 1 .  
     
     
         9 . A peptide fragment of the protein according to  claim 1 .  
     
     
         10 . A DNA specifically hybridizing with the DNA comprising the nucleotide sequence as set forth in SEQ ID NO: 1 and comprises at least 15 nucleotides.  
     
     
         11 . A method for screening a compound binding to the protein according to  claim 1 , the method comprising 
 (a) contacting the protein of  claim 1  or its fragment with a test sample,    (b) detecting the binding activity of the test sample to the protein or its fragment, and    (c) selecting a compound that binds to the protein or its fragment.    
     
     
         12 . A compound that is isolable by the method according to  claim 11  and binds to the protein of  claim 1 .  
     
     
         13 . A method for screening a compound that interferes with the activity of the protein according to  claim 1  to suppress proliferation of lympho-hematopoietic cells, the method comprising 
 (a) contacting the protein according to  claim 1  with lympho-hematopoietic cells in the presence of a test sample,  
 (b) detecting the proliferation of the cells, and  
 (c) selecting a compound that interferes with the activity of the protein according to  claim 1  to suppress proliferation of lympho-hematopoietic cells as compared with a control where the detection is performed in the absence of the test compound.  
 
     
     
         14 . The method according to  claim 13 , wherein said lympho-hematopoietic cells are selected from the group consisting of B lineage cell lines, 1A9, BC7.12, BC7.7, F10, 2E8, 18-81, 7OZ/3, WEHI231 and SP2/0, T lineage lymphoma cell line BW1597, and myelomonocytic leukemia cell line WEHI3.  
     
     
         15 . A compound isolable by the method according to  claim 13 , which interferes with the activity of the protein according to  claim 1  to suppress proliferation of lympho-hematopoietic cells.  
     
     
         16 . A pharmaceutical composition comprising the protein according to  claim 1  as an active ingredient.  
     
     
         17 . The pharmaceutical composition according to  claim 16 , wherein the composition is for treating lympho-hematopoietic disorders.  
     
     
         18 . A pharmaceutical composition comprising the compound according to  claim 12  as an active ingredient.