Fibroblast growth factor homologous factors (FHFs) and methods of use

Abstract

The invention provides fibroblast growth factor homologous factor (FHF) polypeptides and nucleic acid molecules that encode them. Also included in the invention are diagnostic and therapeutic methods using FHF polypeptides and nucleic acids.

1 . A substantially pure fibroblast growth factor homologous factor (FHF) polypeptide.  
     
     
         2 . The polypeptide of  claim 1 , wherein the polypeptide: 
 a. is about 225-250 amino acids in length;    b. lacks an amino terminal signal sequence; and    c. contains a nuclear localization signal.    
     
     
         3 . The polypeptide of  claim 1 , wherein the polypeptide comprises a segment of at least five consecutive amino acids that are conserved in the amino acid sequences of FHF-1 (SEQ ID NO:1), FHF-2 (SEQ ID NO:2), FHF-3 (SEQ ID NO:3), and FHF-4 (SEQ ID NO:4).  
     
     
         4 . The polypeptide of  claim 3 , wherein the segment comprises at least five amino acids of the sequence of SEQ ID NO:22.  
     
     
         5 . The polypeptide of  claim 3 , wherein the segment comprises at least five amino acids of the sequence of SEQ ID NO:24.  
     
     
         6 . The polypeptide of  claim 1 , wherein the polypeptide is FHF-4.  
     
     
         7 . The polypeptide of  claim 1 , wherein the polypeptide comprises the amino acid sequence of FIG. 8 (SEQ ID NO:4).  
     
     
         8 . An isolated nucleic acid encoding the FHF polypeptide of  claim 1 .  
     
     
         9 . The nucleic acid of  claim 8 , wherein the sequence of the nucleic acid comprises the nucleotide sequence of FIG. 8 (SEQ ID NO:21).  
     
     
         10 . The nucleic acid of  claim 8 , wherein the sequence of the nucleic acid is selected from the group consisting of: 
 a. the nucleotide sequence of FIG. 8 (SEQ ID NO:21), where T can also be U;    b. a nucleic acid sequence that hybridizes to the complement of the nucleotide sequence of FIG. 8 (SEQ ID NO:21); and    c: a fragment of a. or b. that comprises at least 15 nucleotides and hybridizes to the complement of the nucleotide sequence of FIG. 8 (SEQ ID NO:21).    
     
     
         11 . A nucleic acid that hybridizes to the nucleic acid of  claim 8 .  
     
     
         12 . A nucleic acid that hybridizes to the nucleic acid of  claim 10 .  
     
     
         13 . The nucleic acid of  claim 8 , wherein the nucleic acid is mammalian.  
     
     
         14 . The nucleic acid of  claim 13 , wherein the nucleic acid is human.  
     
     
         15 . An expression vector containing the nucleic acid of  claim 8 .  
     
     
         16 . The vector of  claim 15 , wherein the vector is a plasmid.  
     
     
         17 . The vector of  claim 15 , wherein the vector is a virus.  
     
     
         18 . A cell stably transformed with the vector of  claim 15 .  
     
     
         19 . An antibody that binds to the FHF polypeptide of  claim 1 .  
     
     
         20 . The antibody of  claim 19 , wherein the antibody is monoclonal.  
     
     
         21 . A method of detecting a cell proliferative disorder associated with expression of the FHF polypeptide of  claim 1 , the method comprising the steps of: 
 a. contacting a specimen from a subject having or suspected of having the disorder with a reagent that detects expression of the FHF polypeptide, and    b. detecting binding of the reagent to the specimen.    
     
     
         22 . The method of  claim 21 , wherein the cell is a brain cell.  
     
     
         23 . The method of  claim 21 , wherein the reagent is an antibody.  
     
     
         24 . The method of  claim 21 , wherein the reagent is a nucleic acid.  
     
     
         25 . The method of  claim 24 , wherein the nucleic acid hybridizes to the nucleic acid of  claim 8 .  
     
     
         26 . The method of  claim 24 , wherein the nucleic acid hybridizes to the complement of the nucleic acid of  claim 8 .  
     
     
         27 . The method of  claim 21 , wherein the detecting is carried out in vivo.  
     
     
         28 . The method of  claim 21 , wherein the detecting is carried out in vitro.  
     
     
         29 . The method of  claim 21 , wherein the reagent comprises a detectable label.  
     
     
         30 . A method of treating a cell proliferative disorder associated with expression of the FHF polypeptide of  claim 1 , the method comprising administering to a subject having or suspected of having the disorder a reagent that suppresses the activity of the FHF polypeptide.  
     
     
         31 . The method of  claim 30 , wherein the reagent is an anti-FHF antibody.  
     
     
         32 . The method of  claim 30 , wherein the reagent is a nucleic acid that hybridizes to the nucleic acid of  claim 8 .  
     
     
         33 . The method of  claim 30 , wherein the cell is a brain cell.  
     
     
         34 . The method of  claim 30 , wherein the reagent is introduced into the cell using a carrier.  
     
     
         35 . The method of  claim 34 , wherein the carrier is a vector.  
     
     
         36 . A method of identifying a nucleic acid encoding an FHF polypeptide, the method comprising probing a sample containing a nucleic acid encoding an FHF polypeptide with an FHF-specific nucleic acid probe.  
     
     
         37 . The method of  claim 36 , wherein the FHF-specific nucleic acid probe hybridizes to: 
 a. a nucleic acid that encodes seven consecutive amino acids, at least four of which are conserved in the amino acid sequences of FHF-1 (SEQ ID NO:1), FHF-2 (SEQ ID NO:2), FHF-3 (SEQ ID NO:3), and FHF-4 (SEQ ID NO:4), or    b. the complementary sequence thereto.