Modulators of intracellular inflammation, cell death and cell survival pathways

Abstract

A B1 protein, its isoforms, analogs, fragments and derivatives, are provided. The protein is useful in the modulation of intracellular inflammation, cell death and/or cell survival pathways.

1 . An isolated polypeptide which potentiates cell death, said polypeptide consisting of: 
 (a) a sequence comprising SEQ ID NO:1;    (b) a sequence comprising an analog of (a) having no more than ten changes in the amino acid sequence of (a), each said change being a substitution, deletion or insertion of a single amino acid, which analog potentiates cell death; or (c) a fragment of the sequence of SEQ ID NO:1, which fragment potentiates cell death.    
     
     
         2 . A polypeptide in accordance with  claim 1 , consisting of a sequence comprising SEQ ID NO:1.  
     
     
         3 . A polypeptide in accordance with  claim 1 , consisting of a sequence comprising an analog of SEQ ID NO:1, having no more than ten changes in the amino acid sequence of SEQ ID NO:1, each said change being a substitution, deletion or insertion of a single amino acid, which analog potentiates cell death.  
     
     
         4 . A polypeptide in accordance with  claim 1  consisting of a fragment of the sequence of SEQ ID NO:1, which fragment potentiates cell death.  
     
     
         5 . An isolated polypeptide in accordance with  claim 1 , wherein said sequence of (b) comprises an analog of (a) having no more than five changes in the amino acid sequence of (a), each said change being a substitution, deletion or insertion of a single amino acid, which analog potentiates cell death.  
     
     
         6 . An isolated polypeptide in accordance with  claim 1 , wherein said sequence of (b) comprises an analog of (a) having no more than three changes in the amino acid sequence of (a), each said change being a substitution, deletion or insertion of a single amino acid, which analog potentiates cell death.  
     
     
         7 . A composition comprising a pharmaceutically acceptable excipient and at least one polypeptide according to  claim 1 .  
     
     
         8 . A method of modulating apoptotic processes or programmed cell death processes (cell death pathways) in which the B1 protein of SEQ ID NO:1 is involved, in cells in need of such modulation, comprising causing one or more polypeptides according to  claim 1  to be disposed within said cells.  
     
     
         9 . A method in accordance with  claim 8 , wherein said causing step comprises introducing into said cells said one or more polypeptide in a form suitable for intracellular introduction thereof.  
     
     
         10 . A method in accordance with  claim 8 , wherein said causing step comprises introducing into said cells a DNA sequence encoding said one or more polypeptide in the form of a suitable vector carrying said sequence, said vector being capable of effecting the ingestion of said sequence into said cells in a way that said sequence is expressed in said cells.  
     
     
         11 . A method of modulating cell survival processes in which the B1 protein of SEQ ID NO:1 is involved, in cells in need of such modulation, comprising causing one or more polypeptides according to  claim 1  to be disposed within said cells.  
     
     
         12 . A method in accordance with  claim 11 , wherein said causing step comprises introducing into said cells said one or more polypeptide in a form suitable for intracellular introduction thereof.  
     
     
         13 . A method in accordance with  claim 11 , wherein said causing step comprises introducing into said cells a DNA sequence encoding said one or more polypeptide in the form of a suitable vector carrying said sequence, said vector being capable of effecting the ingestion of said sequence into said cells in a way that said sequence is expressed in said cells.