title: Proteasome activity influences UV-mediated subnuclear localization changes of NPM.
abstract: UV damage activates cellular stress signaling pathways, causes DNA helix distortions and inhibits transcription by RNA polymerases I and II. In particular, the nucleolus, which is the site of RNA polymerase I transcription and ribosome biogenesis, disintegrates following UV damage. The disintegration is characterized by reorganization of the subnucleolar structures and change of localization of many nucleolar proteins. Here we have queried the basis of localization change of nucleophosmin (NPM), a nucleolar granular component protein, which is increasingly detected in the nucleoplasm following UV radiation. Using photobleaching experiments of NPM-fluorescent fusion protein in live human cells we show that NPM mobility increases after UV damage. However, we show that the increase in NPM nucleoplasmic abundance after UV is independent of UV-activated cellular stress and DNA damage signaling pathways. Unexpectedly, we find that proteasome activity affects NPM redistribution. NPM nucleolar expression was maintained when the UV-treated cells were exposed to proteasome inhibitors or when the expression of proteasome subunits was inhibited using RNAi. However, there was no evidence of increased NPM turnover in the UV damaged cells, or that ubiquitin or ubiquitin recycling affected NPM localization. These findings suggest that proteasome activity couples to nucleolar protein localizations in UV damage stress.
authors.affiliation: Molecular Cancer Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Henna M
authors.initials: HM
authors.lastname: Moore
authors.forename: Baoyan
authors.initials: B
authors.lastname: Bai
authors.forename: Olli
authors.initials: O
authors.lastname: Matilainen
authors.forename: Laureen
authors.initials: L
authors.lastname: Colis
authors.forename: Karita
authors.initials: K
authors.lastname: Peltonen
authors.forename: Marikki
authors.initials: M
authors.lastname: Laiho
mesh_terms: D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects / Q000528:radiation effects; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects; D025801:Ubiquitin / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D061988:Proteasome Inhibitors; D012335:RNA, Ribosomal; D025801:Ubiquitin; D000090243:Nucleophosmin; D046988:Proteasome Endopeptidase Complex
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