Nuclear Integration of Glucocorticoid Receptor and Nuclear Factor-κB Signaling by CREB-binding Protein and Steroid Receptor Coactivator-1

• Published in: The Journal of biological chemistry Vol. 273; no. 45; pp. 29291 - 29294
• Main Authors: Sheppard, Kelly-Ann, Phelps, Kathleen M., Williams, Amy J., Thanos, Dimitris, Glass, Christopher K., Rosenfeld, Michael G., Gerritsen, Mary E., Collins, Tucker
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 06.11.1998
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.45.29291

The p65 (RelA) component of nuclear factor-κB (NF-κB) 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 receptor coactivator-1 (SRC-1) for maximal activity. Here we show that increased levels of CBP relieves the inhibition of glucocorticoid-mediated repression of NF-κB activity and the NF-κB-mediated repression of GR activity. SRC-1 can relieve the NF-κB-mediated repression of GR activity. We propose that cross-talk between the p65 component of NF-κB 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.