title: Gradual reduction in rRNA transcription triggers p53 acetylation and apoptosis via MYBBP1A.
abstract: The nucleolus, whose primary function is ribosome biogenesis, plays an essential role in p53 activation. Ribosome biogenesis is inhibited in response to cellular stress and several nucleolar proteins translocate from the nucleolus to the nucleoplasm, where they activate p53. In this study, we analysed precisely how impaired ribosome biogenesis regulates the activation of p53 by depleting nucleolar factors involved in rRNA transcription or rRNA processing. Nucleolar RNA content decreased when rRNA transcription was inhibited. In parallel with the reduced levels of nucleolar RNA content, the nucleolar protein Myb-binding protein 1 A (MYBBP1A) translocated to the nucleoplasm and increased p53 acetylation. The acetylated p53 enhanced p21 and BAX expression and induced apoptosis. In contrast, when rRNA processing was inhibited, MYBBP1A remained in the nucleolus and nonacetylated p53 accumulated, causing cell cycle arrest at the G1 phase by inducing p21 but not BAX. We propose that the nucleolus functions as a stress sensor to modulate p53 protein levels and its acetylation status, determining cell fate between cell cycle arrest and apoptosis by regulating MYBBP1A translocation.
authors.affiliation: 1] Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennnoudai, Tsukuba 305-8577, Japan [2] First Department of Internal Medicine, Nara Medical University, 840 Shijo-cho Kashihara, Nara 634-8522, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kumazawa
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennnoudai, Tsukuba 305-8577, Japan.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennnoudai, Tsukuba 305-8577, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Katagiri
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennnoudai, Tsukuba 305-8577, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennnoudai, Tsukuba 305-8577, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennnoudai, Tsukuba 305-8577, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Kimura
mesh_terms: D000107:Acetylation; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D012335:RNA, Ribosomal / Q000235:genetics*; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C027624:ribosomal protein L11