P53-MEDIATED REPRESSION OF NUCLEAR FACTOR-KAPPA-B RELA VIA THE TRANSCRIPTIONAL INTEGRATOR P300

The p53 tumor suppressor gene plays an instrumental role in transcript ional regulation of target genes involved in cellular stress responses . p53-dependent transactivation and transrepression require its intera ction with p300/CBP, a coactivator that also interacts with the RelA s ubunit of nuclear factor-kappa B, We find that p53 inhibits RelA-depen dent transactivation without altering RelA expression or inducible kap pa B-DNA binding. p53-mediated repression of RelA is relieved by p300 overexpression and the increased RelA activity conferred by p53-defici ency is counteracted by either transactivation domain-deficient p300 f ragments that bind RelA or a transdominant mutant of I kappa B alpha. Our results suggest that p53 can regulate diverse kappa B-dependent ce llular responses.