title: Nucleophosmin/B23 regulates ubiquitin dynamics in nucleoli by recruiting deubiquitylating enzyme USP36.
abstract: The nucleolus is a subnuclear compartment with multiple cellular functions, including ribosome biogenesis. USP36 is a deubiquitylating enzyme that localizes to nucleoli and plays an essential role in regulating the structure and function of the organelle. However, how the localization of USP36 is regulated remains unknown. Here, we identified a short stretch of basic amino acids (RGKEKKIKKFKREKRR) that resides in the C-terminal region of USP36 and serves as a nucleolar localization signal for the protein. We found that this motif interacts with a central acidic region of nucleophosmin/B23, a major nucleolar protein involved in various nucleolar functions. Knockdown of nucleophosmin/B23 resulted in a significant reduction in the amount of USP36 in nucleoli, without affecting the cellular USP36 level. This was associated with elevated ubiquitylation levels of fibrillarin, a USP36 substrate protein in nucleoli. We conclude that nucleophosmin/B23 recruits USP36 to nucleoli, thereby serving as a platform for the regulation of nucleolar protein functions through ubiquitylation/deubiquitylation.
authors.affiliation: Department of Biological Sciences, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Endo
authors.affiliation: Department of Biological Sciences, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kitamura
authors.affiliation: Department of Biological Sciences, Tokyo Institute of Technology, Yokohama 226-8501, Japan. Electronic address: makomada@bio.titech.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Komada
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002466:Cell Nucleolus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C501066:USP36 protein, human; D025801:Ubiquitin; D000090243:Nucleophosmin; D043222:Ubiquitin Thiolesterase
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