title: SMT3IP1, a nucleolar SUMO-specific protease, deconjugates SUMO-2 from nucleolar and cytoplasmic nucleophosmin.
abstract: Sumoylation is reversibly regulated by SUMO-specific proteases. We characterized a nucleolar SUMO-specific protease, SMT3IP1, which has a preference for SUMO-2/3. To elucidate SMT3IP1 function, we screened for its interacting proteins that may be its substrates or regulate its activity. By using yeast two-hybrid screening, we identified nucleophosmin (NPM) as an SMT3IP1-binding partner. SMT3IP1 could preferentially remove SUMO-2 from sumoylated NPM. A catalytically inactive SMT3IP1 mutant increased intracellular accumulation of SUMO-2-modified NPM in a dominant-negative manner. Sumoylation of cytoplasmic mutated NPM was markedly elevated in an ARF-dependent manner. Despite the divergence in their localization, ectopic expression of SMT3IP1 could desumoylate a SUMO-2-modified NPM mutant. Additionally, genotoxic drugs caused the dissociation of NPM from nucleolar co-localization with SMT3IP1, but did not affect desumoylation of NPM by SMT3IP1. Our findings suggest that SMT3IP1-mediated desumoylation might control NPM physiological functions at both the nucleolus and other subcellular compartments.
authors.affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Tsu 514-8507, Japan. nishida@gene.mie-u.ac.jp
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Nishida
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002166:Camptothecin / Q000633:toxicity; D002460:Cell Line; D002466:Cell Nucleolus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D004249:DNA Damage; D003609:Dactinomycin / Q000633:toxicity; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D000090243:Nucleophosmin; D003609:Dactinomycin; D010450:Endopeptidases; C416522:Smt3-specific isopeptidase 1; D002166:Camptothecin