Wadgaonkar R, Phelps K M, Haque Z, Williams A J, Silverman E S, Collins T
Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
J Biol Chem. 1999 Jan 22;274(4):1879-82. doi: 10.1074/jbc.274.4.1879.
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.
转录共激活因子可能通过协调多种信号事件发挥核整合器的作用。在此我们表明，核因子-κB（NF-κB）的p65（RelA）组分与p53相互抑制对方激活转录的能力。此外，紫外线诱导的p53可抑制肿瘤坏死因子激活的NF-κB。p65和p53的最大活性均依赖于共激活因子CREB结合蛋白（CBP）。共激活因子水平的升高可缓解p53介导的对NF-κB活性的抑制以及p65介导的对p53依赖性基因表达的抑制。对有限量CBP的核内竞争为改变NF-κB依赖性增殖或存活基因与参与细胞周期停滞和凋亡的p53依赖性基因表达之间的平衡提供了一种新机制。
