title: p53 Transcriptional activity is mediated through the SRC1-interacting domain of CBP/p300.
abstract: The tumor suppressor p53 recruits the cellular coactivator CBP/p300 to mediate the transcriptional activation of target genes. In this study, we identify a novel p53-interacting region in CBP/p300, which we call CR2, located near the carboxyl terminus. The 95-amino acid CR2 region (amino acids 2055--2150) is located adjacent to the C/H3 domain and corresponds precisely with the minimal steroid receptor coactivator 1 (SRC1)-interacting domain of CBP (also called IBiD). We show that the region of p53 that participates in the CR2 interaction resides within the first 107 amino acids of the protein. p53 binds strongly to the CR2 domain of both CBP and the highly homologous coactivator p300. Importantly, an in-frame deletion of CR2 within the full-length p300 protein strongly compromises p300-mediated p53 transcriptional activation from a chromatin template in vitro. The identification of the p53-interacting CR2 domain in CBP/p300 prompted us to ask if the human T-cell leukemia virus (HTLV-I) Tax protein, which also interacts with CR2, competes with p53 for binding to this domain. We show that p53 and Tax exhibit mutually exclusive binding to the CR2 region, possibly contributing to the previously reported Tax repression of p53 function. Together, these studies identify and molecularly characterize a new p53 binding site on CBP/p300 that participates in coactivator-mediated p53 transcription function. The identity of the p53.CR2 interaction indicates that at least three distinct sites on CBP/p300 may participate in mediating p53 transactivation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870, USA.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Livengood
authors.forename: Kirsten E S
authors.initials: KE
authors.lastname: Scoggin
authors.forename: Karen
authors.initials: K
authors.lastname: Van Orden
authors.forename: Steven J
authors.initials: SJ
authors.lastname: McBryant
authors.forename: Rajeswari S
authors.initials: RS
authors.lastname: Edayathumangalam
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Laybourn
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Nyborg
mesh_terms: D001665:Binding Sites; D001667:Binding, Competitive; D002471:Cell Transformation, Neoplastic; D016356:Gene Products, tax / Q000378:metabolism; D051548:Histone Acetyltransferases; D006801:Humans; D019169:Jurkat Cells; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D056920:Nuclear Receptor Coactivator 1; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000502:physiology*
chemical_list: D016356:Gene Products, tax; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1