CREB-binding protein is a nuclear integrator of nuclear factor-κB and p53 signaling

Transcriptional coactivators may function as nuclear integrators by coordinating diverse signaling events. Here we show that the p65 (RelA) component of nuclear factor-kappa B (NF-kappa B) and p53 mutually repress each other's ability to activate transcription. Additionally, tumor necrosis factor-activated NP-kappa B is inhibited by UV light-induced p53. Both p65 and p53 depend upon the coactivator CREB-binding protein (CBP) for maximal activity. Increased levels of the coactivator relieve p53-mediated repression of NF-kappa B activity and p65-mediated repression of p53-dependent gene expression. Nuclear competition for limiting amounts of CBP provides a novel mechanism for altering the balance between the expression of NF-kappa B-dependent proliferation or survival genes and p53-dependent genes involved in cell cycle arrest and apoptosis.