title: The nucleolar protein nucleophosmin is essential for autophagy induced by inhibiting Pol I transcription.
abstract: Various cellular stresses activate autophagy, which is involved in lysosomal degradation of cytoplasmic materials for maintaining nutrient homeostasis and eliminating harmful components. Here, we show that RNA polymerase I (Pol I) transcription inhibition induces nucleolar disruption and autophagy. Treatment with autophagy inhibitors or siRNA specific for autophagy-related (ATG) proteins inhibited autophagy but not nucleolar disruption induced by Pol I transcription inhibition, which suggested that nucleolar disruption was upstream of autophagy. Furthermore, treatment with siRNA specific for nucleolar protein nucleophosmin (NPM) inhibited this type of autophagy. This showed that NPM was involved in autophagy when the nucleolus was disrupted by Pol I inhibition. In contrast, NPM was not required for canonical autophagy induced by nutrient starvation, as it was not accompanied by nucleolar disruption. Thus, our results revealed that, in addition to canonical autophagy, there may be NPM-dependent autophagy associated with nucleolar disruption.
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: Center of Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennnoudai, Tsukuba 305-8577, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kuroda
authors.affiliation: 1] Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennnoudai, Tsukuba 305-8577, Japan [2] Center of Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennnoudai, Tsukuba 305-8577, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishimoto
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: 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: Keiji
authors.initials: K
authors.lastname: Kimura
mesh_terms: D001343:Autophagy / Q000235:genetics*; D002466:Cell Nucleolus / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D009697:Nucleolus Organizer Region / Q000235:genetics; D000090243:Nucleophosmin; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors / Q000235:genetics*; D034741:RNA, Small Interfering; D014158:Transcription, Genetic
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D000090243:Nucleophosmin; D012318:RNA Polymerase I