Compositions and methods for modulating c-rel-dependent cytokine production

Abstract

The present invention is directed to compositions and methods for modulating c-Rel-dependent cytokine production without materially altering the level of expression of NFκB and/or the amount of IκB. The present invention is also directed to screening for modulators of c-Rel activity as determined by assaying for altered subcellular localization of c-Rel but where the level of expression of NFκB and/or the amount of IκB is materially unaltered.

1 - 16 . (canceled) 
     
     
         17 . A method of identifying a molecule that selectively alters the subcellular location of c-Rel in the nucleus of a cell, but not p65, comprising:
 (a) contacting the cell with a candidate molecule;   (b) detecting localization of c-Rel in the nucleus of the cell; and   (c) determining localization of p65 in the nucleus of the cell;   
       wherein a decrease in the amount of c-Rel, but not p65, localized to the nucleus without a material alteration in the level of expression of c-Rel and/or amount of I K B relative to said amount in a cell not so contacted with the candidate molecule indicates that the candidate molecule selectively alters the subcellular localization of c-Rel. 
     
     
         18 . The method according to claim  16 , wherein step (b) comprises contacting the cell with an antibody to c-Rel or a binding region of said antibody, and a fluorescently labeled binding partner of said antibody under conditions that allow for immunospecific binding. 
     
     
         19 . The method according to claim  16 , wherein step (b) comprises contacting the cell with a fluorescently labeled antibody to c-Rel or a binding region of said antibody under conditions that allow for immunospecific binding. 
     
     
         20 . The method according to claim  16 , wherein step (b) comprises detection of c-Rel localization in the nucleus by sequencing by mass spectroscopy nuclear proteins isolated from the cell. 
     
     
         21 . The method according to claim  16 , wherein the cell is a cultured cell. 
     
     
         22 . The method according to claim  16 , wherein step (c) comprises determination of p65 localization in the nucleus by immunoblotting. 
     
     
         23 . The method according to claim  16 , wherein step (c) comprises determination of p65 localization in the nucleus by densitometry.