CREB-binding protein is a nuclear integrator of nuclear factor-kappa B andp53 signaling

Transcriptional coactivators may function as nuclear integrators by coordin ating 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-ac tivated NP-kappa B is inhibited by UV light-induced p53. Both p65 and p53 d epend 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 expressi on. Nuclear competition for limiting amounts of CBP provides a novel mechan ism for altering the balance between the expression of NF-kappa B-dependent proliferation or survival genes and p53-dependent genes involved in cell c ycle arrest and apoptosis.