Fusion polypeptide suitable as a cytotoxin

Abstract

The present invention relates to fusion polypeptides including (a) a binding site for a cytoskeleton component and (b 1 ) an effector protein or the catalytic domain thereof or (b 2 ) a binding site for the effector protein, and nucleic acid sequences encoding the fusion polypeptides. Moreover, various therapeutic uses of the fusion polypeptides are described, e.g., the treatment of diseases associated with the presence of an aberrant cell population, preferably cancer or AIDS.

1 . A fusion polypeptide comprising (a) a binding site for a cytoskeleton component and (b 1 ) an effector protein or the catalytic domain therof or (b 2 ) a binding site for said effector protein.  
     
     
         2 . The fusion polypeptide of  claim 1 , wherein both parts (a) and (b) of the fusion polypeptide are linked by a peptide linker.  
     
     
         3 . The fusion polypeptide of  claim 2 , wherein said peptide linker is EGFP (SEQ ID NO: 1).  
     
     
         4 . The fusion polypeptide of  claim 1 , wherein said cytoskeleton component is tropomyosin, gelsolin or tubulin.  
     
     
         5 . The fusion polypeptide of  claim 1 , wherein said binding site is derived from parvovirus NS1.  
     
     
         6 . The fusion polypeptide of  claim 5 , wherein said binding site comprises the amino acid sequence from positions 235 to 358 of NS1.  
     
     
         7 . The fusion polypeptide of  claim 1 , wherein said effector protein is a protein kinase.  
     
     
         8 . The fusion polypeptide of  claim 7 , wherein said protein kinase is casein kinase II (CKIIα).  
     
     
         9 . The fusion polypeptide of  claim 7 , wherein said binding site for casein kinase II (CKIIα) comprises the amino acid sequence DLEPDEELED (SEQ ID NO: 2).  
     
     
         10 . The fusion polypeptide of  claim 1 , wherein in parts (a) and/or (b) modifications are present required for inducing and/or enhancing morphological changes of the host cell.  
     
     
         11 . A nucleic acid sequence encoding the fusion polypeptide of  claim 1 .  
     
     
         12 . A recombinant vector containing the nucleic acid sequence of  claim 11 .  
     
     
         13 . The recombinant vector of  claim 12 , wherein the nucleic acid sequence is operatively linked to regulatory elements allowing transcription and synthesis of a translatable RNA in prokaryotic and/or eukaryotic host cells.  
     
     
         14 . A recombinant host cell which contains the recombinant vector of  claim 12 .  
     
     
         15 . The recombinant host cell of  claim 14 , which is a mammalian cell, a bacterial cell, an insect cell or a yeast cell.  
     
     
         16 . A non-human transgenic animal comprising the nucleic acid molecule of  claim 11 .  
     
     
         17 . An antibody that binds specifically to the fusion polypeptide of  claim 1 .  
     
     
         18 . The antibody of  claim 17  which is detectably labelled.  
     
     
         19 . The antibody of  claim 18 , wherein the label is a radioisotope, a bioluminescent compound, a chemiluminescent compound, a fluorescent compound, a metal chelate, or an enzyme.  
     
     
         20 . A pharmaceutical composition containing the fusion polypeptide of  claim 1  or a nucleic acid sequence that encodes for such fusion polypeptide.  
     
     
         21 . A method for the treatment of a disease associated with the presence of an aberrant cell population, the method comprising administering a therapeutic amount of the composition of  claim 20 .  
     
     
         22 . The method according to  claim 21 , wherein said disease is cancer or AIDS.  
     
     
         23 . A fusion polypeptide comprising (a) a tropomyosin binding fragment of Minuter virus of Mice (MVM) non-structural protein (NS)-1, and (b 1 ) catalytic domain of casein kinase II-alpha (CKIIα) or (b 2 ) a binding site for (CKIIα).