Gene regulatory peptides

Abstract

The invention relates to the modulation of gene expression in a cell, also called gene control, in particular in relation to the treatment of a variety of diseases. The invention provides a method for modulating expression of a gene in a cell comprising providing the cell with a signaling molecule comprising a peptide or functional analogue thereof. Furthermore, the invention provides a method for identifying or obtaining a signaling molecule comprising a peptide or functional derivative or analogue thereof capable of modulating expression of a gene in a cell comprising providing the cell with a peptide or derivative or analogue thereof and determining the activity and/or nuclear translocation of a gene transcription factor.

1 . A method for modulating expression of a gene in a cell, the method comprising: 
 providing said cell with a signaling molecule comprising a peptide or functional analogue or derivative thereof.    
     
     
         2 . The method according to  claim 1 , wherein said peptide is selected from the group consisting of LQG (SEQ ID NO:29), AQG (SEQ ID NO:30), LQGV (SEQ ID NO:6), AQGV (SEQ ID NO:12), LQGA (SEQ ID NO:31), VLPALP (SEQ ID NO:10), ALPALP (SEQ ID NO:33), VAPALP (SEQ ID NO:34), ALPALPQ (SEQ ID NO:35), VLPAAPQ (SEQ ID NO:36), VLPALAQ (SEQ ID NO:37), LAGV (SEQ ID NO:38), VLAALP (SEQ ID NO:39), VLPALA (SEQ ID NO:40), VLPALPQ (SEQ ID NO:41), VLAALPQ (SEQ ID NO:42), VLPALPA (SEQ ID NO:43), GVLPALP (SEQ ID NO:44), LQGVLPALPQVVC (SEQ ID NO:46), LPGCPRGVNPVVS (SEQ ID NO:52), LPGC (SEQ ID NO:53), MTRV (SEQ ID NO:54), MTR (SEQ ID NO:55), VVC (SEQ ID NO:56), and mixtures thereof.  
     
     
         3 . The method according to  claim 1 , wherein said signaling molecule modulates translocation and/or activity of a gene transcription factor.  
     
     
         4 . The method according to  claim 3 , wherein said gene transcription factor is an NF-kappaB/Rel protein.  
     
     
         5 . A method for identifying or obtaining a signaling molecule capable of modulating expression of a gene in a cell, said method comprising: 
 providing said cell with a peptide or derivative or analogue thereof, and    determining activity and/or nuclear translocation of a gene transcription factor to thus identify or obtain a signaling molecule capable of modulating expression of a gene in a cell.    
     
     
         6 . The method according to  claim 5 , further comprising determining whether said signaling molecule is membrane-permeable.  
     
     
         7 . The method according to  claim 5  wherein said gene transcription factor comprises an NF-kappaB/Rel protein.  
     
     
         8 . The method according to  claim 5 , further comprising determining relative up-regulation and/or down-regulation of at least one gene expressed in said cell.  
     
     
         9 . A method for identifying or obtaining a signaling molecule capable of modulating expression of a gene in a cell, said method comprising: 
 providing said cell with a peptide or derivative or analogue thereof, and    determining relative up-regulation and/or down-regulation of at least one gene expressed in said cell.    
     
     
         10 . The method according to  claim 9 , further comprising determining relative up-regulation and/or down-regulation of multiple genes expressed in said cell.  
     
     
         11 . A method for identifying or obtaining a signaling molecule capable of modulating expression of a gene in a cell, said method comprising: 
 providing a peptide or derivative or analogue thereof, and    determining binding of said peptide or derivative or analogue thereof to a factor related to gene control.    
     
     
         12 . The method according to  claim 11 , further comprising providing multiple peptides or derivatives or analogues thereof and determining binding of at least one of said peptides or derivatives or analogues thereof to said factor related to gene control.  
     
     
         13 . The method according to  claim 11 , wherein said factor related to gene control comprises a transcription factor.  
     
     
         14 . The method according to  claim 13 , wherein said transcription factor comprises an NF-kappaB-Rel protein.  
     
     
         15 . The method according to  claim 11 , further comprising providing a cell with said peptide or derivative or analogue thereof and determining activity and/or nuclear translocation of a gene transcription factor in said cell.  
     
     
         16 . The method according to  claim 11 , further comprising providing a cell with said peptide or derivative or analogue thereof and determining relative up-regulation and/or down-regulation of at least one gene expressed in said cell.  
     
     
         17 . A signaling molecule useful in modulating expression of a gene in a cell and identifiable or obtainable by employing the method according to  claim 5 .  
     
     
         18 . The signaling molecule of  claim 17 , wherein said signaling molecule is selected from the group consisting of LQG (SEQ ID NO:29), AQG (SEQ ID NO:30), LQGV (SEQ ID NO:6), AQGV (SEQ ID NO:12), LQGA (SEQ ID NO:31), VLPALP (SEQ ID NO:10), ALPALP (SEQ ID NO:33), VAPALP (SEQ ID NO:34), ALPALPQ (SEQ ID NO:35), VLPAAPQ (SEQ ID NO:36), VLPALAQ (SEQ ID NO:37), LAGV (SEQ ID NO:38), VLAALP (SEQ ID NO:39), VLPALA (SEQ ID NO:40), VLPALPQ (SEQ ID NO:41), VLAALPQ (SEQ ID NO:42), VLPALPA (SEQ ID NO:43), GVLPALP (SEQ ID NO:44), LQGVLPALPQVVC (SEQ ID NO:46), LPGCPRGVNPVVS (SEQ ID NO:52), LPGC (SEQ ID NO:53), MTRV (SEQ ID NO:54), MTR (SEQ ID NO:55), VVC (SEQ ID NO:56), functional analogues, derivatives thereof, and mixtures thereof.  
     
     
         19 . A signaling molecule capable of modulating expression of a gene in a cell comprising a peptide of at most 30 amino acids or a functional analogue or derivative thereof.  
     
     
         20 . The signaling molecule of  claim 19 , wherein said peptide is an oligopeptide of from about 3 to at about 15 amino acids long.  
     
     
         21 . An inhibitor of NF-kappaB/Rel protein activation comprising the signaling molecule of  claim 17 .  
     
     
         22 . A composition comprising the signaling molecule of  claim 17  in an amount sufficient to modulate gene expression by inhibiting NF-kappaB/Rel protein activation.