The p53 tumor suppressor gene plays an instrumental role in transcriptional regulation of target genes involved in cellular stress responses. p53-dependent transactivation and transrepression require its interaction with p300/CBP, a coactivator that also interacts with the RelA subunit of nuclear factor-κB. We find that p53 inhibits RelA-dependent transactivation without altering RelA expression or inducible κB-DNA binding. p53-mediated repression of RelA is relieved by p300 overexpression and the increased RelA activity conferred by p53-deficiency is counteracted by either transactivation domain-deficient p300 fragments that bind RelA or a transdominant mutant of IκBα. Our results suggest that p53 can regulate diverse κB-dependent cellular responses.
Funded by Grant 1 R29CA71660-01A1 from the National Cancer Institute and Grant R21 CA/ES66204 from the NIH (to A. B.). A. B. is a recipient of a Passano Physician Scientist award, a Valvano Foundation Scholar award, a Jose Carreras American Society of Hematology Scholar award, and grants from the American Cancer Society.