title: p53-mediated repression of nuclear factor-kappaB RelA via the transcriptional integrator p300.
abstract: 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-kappaB. We find that p53 inhibits RelA-dependent transactivation without altering RelA expression or inducible kappaB-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 IkappaB alpha. Our results suggest that p53 can regulate diverse kappaB-dependent cellular responses.
authors.affiliation: Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-8967, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ravi
authors.forename: B
authors.initials: B
authors.lastname: Mookerjee
authors.forename: Y
authors.initials: Y
authors.lastname: van Hensbergen
authors.forename: G C
authors.initials: GC
authors.lastname: Bedi
authors.forename: A
authors.initials: A
authors.lastname: Giordano
authors.forename: W S
authors.initials: WS
authors.lastname: El-Deiry
authors.forename: E J
authors.initials: EJ
authors.lastname: Fuchs
authors.forename: A
authors.initials: A
authors.lastname: Bedi
mesh_terms: D050882:CREB-Binding Protein; D004247:DNA / Q000378:metabolism; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D008025:Ligases / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000737:chemistry; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D016328:NF-kappa B; D009687:Nuclear Proteins; D015534:Trans-Activators; D004247:DNA; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases