title: The nucleolar protein Myb-binding protein 1A (MYBBP1A) enhances p53 tetramerization and acetylation in response to nucleolar disruption.
abstract: Tetramerization of p53 is crucial to exert its biological activity, and nucleolar disruption is sufficient to activate p53. We previously demonstrated that nucleolar stress induces translocation of the nucleolar protein MYBBP1A from the nucleolus to the nucleoplasm and enhances p53 activity. However, whether and how MYBBP1A regulates p53 tetramerization in response to nucleolar stress remain unclear. In this study, we demonstrated that MYBBP1A enhances p53 tetramerization, followed by acetylation under nucleolar stress. We found that MYBBP1A has two regions that directly bind to lysine residues of the p53 C-terminal regulatory domain. MYBBP1A formed a self-assembled complex that provided a molecular platform for p53 tetramerization and enhanced p300-mediated acetylation of the p53 tetramer. Moreover, our results show that MYBBP1A functions to enhance p53 tetramerization that is necessary for p53 activation, followed by cell death with actinomycin D treatment. Thus, we suggest that MYBBP1A plays a pivotal role in the cellular stress response.
authors.affiliation: From the Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8577, Japan.
authors.forename: Wakana
authors.initials: W
authors.lastname: Ono
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Wataru
authors.initials: W
authors.lastname: Yokoyama
authors.forename: Takao
authors.initials: T
authors.lastname: Kuroda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Ichiaki
authors.initials: I
authors.lastname: Ito
authors.forename: Keiji
authors.initials: K
authors.lastname: Kimura
authors.forename: Kensuke
authors.initials: K
authors.lastname: Akaogi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Waku
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
mesh_terms: D000107:Acetylation; D001665:Binding Sites; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000378:metabolism*; D004268:DNA-Binding Proteins; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human
keywords: Cell Death; Nucleolus; Post-translational Modification; Stress Response; p300; p53