title: Novel nucleolar pathway connecting intracellular energy status with p53 activation.
abstract: In response to a shortage of intracellular energy, mammalian cells reduce energy consumption and induce cell cycle arrest, both of which contribute to cell survival. Here we report that a novel nucleolar pathway involving the energy-dependent nucleolar silencing complex (eNoSC) and Myb-binding protein 1a (MYBBP1A) is implicated in these processes. Namely, in response to glucose starvation, eNoSC suppresses rRNA transcription, which results in a reduction in nucleolar RNA content. As a consequence, MYBBP1A, which is anchored to the nucleolus via RNA, translocates from the nucleolus to the nucleoplasm. The translocated MYBBP1A induces acetylation and accumulation of p53 by enhancing the interaction between p300 and p53, which eventually leads to the cell cycle arrest (or apoptosis). Taken together, our results indicate that the nucleolus works as a sensor that transduces the intracellular energy status into the cell cycle machinery.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8577, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kumazawa
authors.forename: Kazuho
authors.initials: K
authors.lastname: Nishimura
authors.forename: Takao
authors.initials: T
authors.lastname: Kuroda
authors.forename: Wakana
authors.initials: W
authors.lastname: Ono
authors.forename: Chie
authors.initials: C
authors.lastname: Yamaguchi
authors.forename: Naohiro
authors.initials: N
authors.lastname: Katagiri
authors.forename: Mai
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masumoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Akiko
authors.initials: A
authors.lastname: Murayama
authors.forename: Keiji
authors.initials: K
authors.lastname: Kimura
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
mesh_terms: D000107:Acetylation; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors