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Sheppard, K.A. et al.

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

The p65 (RelA) component of nuclear factor-kappaB (NF-kappaB) 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-kappaB activity and the NF-kappaB-mediated repression of GR activity. SRC-1 can relieve the NF-kappaB-mediated repression of GR activity. We propose that cross-talk between the p65 component of NF-kappaB 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.[1]

References

Nuclear integration of glucocorticoid receptor and nuclear factor-kappaB signaling by CREB-binding protein and steroid receptor coactivator-1. Sheppard, K.A., Phelps, K.M., Williams, A.J., Thanos, D., Glass, C.K., Rosenfeld, M.G., Gerritsen, M.E., Collins, T. J. Biol. Chem. (1998) [Pubmed]

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