La actividad transcripcional de NF-kB es diferencialmente regulada por dominios especificos del coactivador TIF2

we have previously shown that nuclear receptor coactivator overexpression significantly enhanced nf-kb activity in a dose response manner. we studied the mechanism by which tif2 regulates nf-kb activity. we determined that: 1) the p38 specific inhibitor reduces 50% nf-kb transcriptional activity, even in cells that overexpress distinct tif2 deletions; 2) there is a physical interaction between tif2 and p38 and rela determined through in vitro translated protein bindind assays; 3) tif2 is a p38 substrate; 4) there is a physical interaction between tif2 and ikk in tnf-a 20 ng/ml stimulated or not hek 293 cell protein extract, and ikb only in basal conditions, determined by binding pull down assays. this nf-kb complex regulates its activity and targets gene expression in a determined physiologic context depending on the coactivator complex content.