title: Nucleolar structure and function are regulated by the deubiquitylating enzyme USP36.
abstract: The nucleolus is a subnuclear compartment and the site of ribosome biogenesis. Previous studies have implicated protein ubiquitylation in nucleolar activity. Here we show that USP36, a deubiquitylating enzyme of unknown function, regulates nucleolar activity in mammalian cells. USP36 localized to nucleoli via the C-terminal region, which contains basic amino acid stretches. Dominant-negative inhibition of USP36 caused the accumulation of ubiquitin-protein conjugates in nucleoli, suggesting that nucleoli are the site of USP36 action. USP36 deubiquitylated the nucleolar proteins nucleophosmin/B23 and fibrillarin, and stabilized them by counteracting ubiquitylation-mediated proteasomal degradation. RNAi-mediated depletion of cellular USP36 resulted in reduced levels of rRNA transcription and processing, a less-developed nucleolar morphology and a slight reduction in the cytoplasmic ribosome level, which eventually led to a reduced rate of cell proliferation. We conclude that by deubiquitylating various nucleolar substrate proteins including nucleophosmin/B23 and fibrillarin, USP36 plays a crucial role in regulating the structure and function of nucleoli.
authors.affiliation: Department of Biological Sciences, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Endo
authors.forename: Masaki
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Inada
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
authors.forename: Naomi
authors.initials: N
authors.lastname: Kitamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Komada
mesh_terms: D000818:Animals; D019556:COS Cells; D002466:Cell Nucleolus / Q000378:metabolism / Q000648:ultrastructure; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000090243:Nucleophosmin; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D012335:RNA, Ribosomal; C501066:USP36 protein, human; D025801:Ubiquitin; C047458:fibrillarin; D000090243:Nucleophosmin; D043222:Ubiquitin Thiolesterase