Nuclear integration of glucocorticoid receptor and nuclear factor-κB signaling by CREB-binding protein and steroid receptor coactivator-1

The p65 (RelA) component of nuclear factor-kappa B (NF-kappa B) and the glucocorticoid receptor (GR) mutually repress each other's ability to activate transcription. Both of these transcriptional activators depend upon the coactivators CREB-binding protein (CBP) and steroid re ceptor coactivator-1 (SRC-1) for maximal activity. Here we show that increased levels of CBP relieves the inhibition of glucocorticoid-mediated repression of NF-kappa B activity and the NF-kappa B-mediated repression of GR activity. SRC-1 can relieve the NF-kappa B-mediated repression of GR activity. We propose that cross-talk between the p65 component of NF-kappa B and glucocorticoid receptors is due, at least in part, to nuclear competition for limiting amounts of the coactivators CBP and SRC-1, thus providing a novel mechanism for decreasing expression of genes involved in the inflammatory response.