Gene regulator

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 said cell with a signalling molecule comprising a peptide or functional analogue thereof. Furthermore, the invention provides a method for identifying or obtaining a signalling molecule comprising a peptide or functional derivative or analogue thereof capable of modulating expression of a gene in a cell comprising providing said cell with a peptide or derivative or analogue thereof and determining the activity and/or nuclear translocation of a gene transcription factor.

What is claimed is:  
     
         1 . A method for obtaining information about the capacity or tendency of an oligopeptide, or a modification or derivative thereof, to regulate expression of a gene comprising the steps of: 
 a) contacting said oligopeptide, or a modification or derivative thereof, with at leaste one cell;    b) determining the presence of at least one gene product in or derived from said cell.    
     
     
         2 . The method according to  claim 1  wherein said oligopeptide comprises an amino acid sequence corresponding to a fragment of a naturally occurring polypeptide.  
     
     
         3 . The method according to  claim 2  wherein said naturally occurring polypeptide comprises human chorionic gonadotropic hormone (hCG).  
     
     
         4 . The method according to any one of  claims 1  to  3  wherein said cell comprises an eukaryotic cell.  
     
     
         5 . The method according to any one of  claims 1  to  4  further comprising 
 c) determining the presence of said gene product in or derived from a cell which has not been contacted with said oligopeptide, or a modification or derivative thereof, and determining the ratio of gene product found in step b to gene product found in step c.  
 
     
     
         6 . A method for identifying or obtaining a signalling molecule comprising a peptide or functional derivative or analogue thereof capable of modulating expression of a gene in a cell comprising providing said cell with a peptide or derivative or analogue thereof and determining the activity and/or nuclear translocation of a gene transcription factor and then synthesising the molecule with the desired activity.  
     
     
         7 . The method according to  claim 6  further comprising determining whether said signalling molecule is membrane-permeable.  
     
     
         8 . The method according to  claim 6  or  7  wherein said gene transcription factor comprises a NF-kappaB/Rel protein.  
     
     
         9 . A method for identifying or obtaining a signalling molecule comprising a peptide or functional derivative or analogue thereof capable of modulating expression of a gene in a cell 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 and then synthesising the molecule with the desired activity.  
     
     
         10 . The method according to  claim 6 ,  7 ,  8  or  9  further comprising determining relative up-regulation and/or down-regulation of at least one gene expressed in said cell.  
     
     
         11 . The method according to  claim 6  to  10  further comprising determining relative up-regulation and/or down-regulation of a multitude of genes expressed in said cell.  
     
     
         12 . A method for identifying or obtaining a signalling molecule comprising a peptide or functional derivative or analogue thereof capable of modulating expression of a gene in a cell 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 and then synthesising the molecule with the desired activity.  
     
     
         13  The method according to  claim 12  further comprising providing a multitude of peptides or derivatives or analogues thereof and determining binding of at least one of said peptides or derivatives or analogues thereof to a factor related to gene control.  
     
     
         14 . The method according to  claim 12  or  13  wherein said factor related to gene control comprises a transcription factor.  
     
     
         15 . The method according to  claim 14  wherein said transcription factor comprises a NF-kappaB-Rel protein.  
     
     
         16 . The method according any one of  claims 12  to  15  further comprising providing a cell with said peptide or derivative or analogue thereof and determining the activity and/or nuclear translocation of a gene transcription factor in said cell.  
     
     
         17 . The method according to any one of  claims 12  to  16  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.  
     
     
         18 . A signalling molecule useful in modulating expression of a gene in a cell and identifiable or obtainable by employing a method according to any one of  claims 1  to  17 .  
     
     
         19 . A signalling molecule according to  claim 18  selected from the group of peptides LQG, AQG, LQGV, AQGV, LQGA, VLPALP, ALPALP, VAPALP, ALPALPQ, VLPAAPQ, VLPALAQ, LAGV, VLAALP, VLAALP, VLPALA, VLPALPQ, VLAALPQ, VLPALPA, GVLPALP, LQGVLPALPQVVC, LPGCPRGVNPVVS, LPGC, MTRV, MTR, VVC, and functional analogues or derivatives thereof.  
     
     
         20 . A signalling 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.  
     
     
         21 . A signalling molecule according to  claim 20  wherein said peptide is an oligopeptide of from about 3 to at about 15 amino acids long.  
     
     
         22 . A modulator of NF-kappaB/Rel protein activation comprising a signalling molecule according to anyone of  claims 18  to  21 .  
     
     
         23 . Use of a signalling molecule according to anyone of  claim 18  to  21  for the production of a pharmaceutical composition for the modulation of gene expression.  
     
     
         24 . Use according to  claim 23  for the modulation of gene expression by inhibiting NF-kappaB/Rel protein activation.