CREB-binding protein is a nuclear integrator of nuclear factor-kappaB 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-kappaB (NF-kappaB) and p53 mutually repress each other's ability to activate transcription. Additionally, tumor necrosis factor-activated NF-kappaB 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-kappaB 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-kappaB-dependent proliferation or survival genes and p53-dependent genes involved in cell cycle arrest and apoptosis.
Wadgaonkar
R
R
Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Phelps
K M
KM
Haque
Z
Z
Williams
A J
AJ
Silverman
E S
ES
Collins
T
T
D000818:Animals; D019556:COS Cells; D050882:CREB-Binding Protein; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival; D005786:Gene Expression Regulation; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays
D016328:NF-kappa B; D009687:Nuclear Proteins; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D050882:CREB-Binding Protein