title: Nucleolar protein, Myb-binding protein 1A, specifically binds to nonacetylated p53 and efficiently promotes transcriptional activation.
abstract: Nucleolar dynamics are important for cellular stress response. We previously demonstrated that nucleolar stress induces nucleolar protein Myb-binding protein 1A (MYBBP1A) translocation from the nucleolus to the nucleoplasm and enhances p53 activity. However, the underlying molecular mechanism is understood to a lesser extent. Here we demonstrate that MYBBP1A interacts with lysine residues in the C-terminal regulatory domain region of p53. MYBBP1A specifically interacts with nonacetylated p53 and induces p53 acetylation. We propose that MYBBP1A dissociates from acetylated p53 because MYBBP1A did not interact with acetylated p53 and because MYBBP1A was not recruited to the p53 target promoter. Therefore, once p53 is acetylated, MYBBP1A dissociates from p53 and interacts with nonacetylated p53, which enables another cycle of p53 activation. Based on our observations, this MYBBP1A-p53 binding property can account for efficient p53-activation by MYBBP1A under nucleolar stress. Our results support the idea that MYBBP1A plays catalytic roles in p53 acetylation and activation.
authors.affiliation: 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: Kensuke
authors.initials: K
authors.lastname: Akaogi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Waku
authors.forename: Takao
authors.initials: T
authors.lastname: Kuroda
authors.forename: Wataru
authors.initials: W
authors.lastname: Yokoyama
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Keiji
authors.initials: K
authors.lastname: Kimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53