title: Ubiquitin-specific protease-like 1 (USPL1) is a SUMO isopeptidase with essential, non-catalytic functions.
abstract: Isopeptidases are essential regulators of protein ubiquitination and sumoylation. However, only two families of SUMO isopeptidases are at present known. Here, we report an activity-based search with the suicide inhibitor haemagglutinin (HA)-SUMO-vinylmethylester that led to the identification of a surprising new SUMO protease, ubiquitin-specific protease-like 1 (USPL1). Indeed, USPL1 neither binds nor cleaves ubiquitin, but is a potent SUMO isopeptidase both in vitro and in cells. C13orf22l--an essential but distant zebrafish homologue of USPL1--also acts on SUMO, indicating functional conservation. We have identified invariant USPL1 residues required for SUMO binding and cleavage. USPL1 is a low-abundance protein that colocalizes with coilin in Cajal bodies. Its depletion does not affect global sumoylation, but causes striking coilin mislocalization and impairs cell proliferation, functions that are not dependent on USPL1 catalytic activity. Thus, USPL1 represents a third type of SUMO protease, with essential functions in Cajal body biology.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schulz
authors.forename: Georgia
authors.initials: G
authors.lastname: Chachami
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kozaczkiewicz
authors.forename: Ulrike
authors.initials: U
authors.lastname: Winter
authors.forename: Nicolas
authors.initials: N
authors.lastname: Stankovic-Valentin
authors.forename: Petra
authors.initials: P
authors.lastname: Haas
authors.forename: Kay
authors.initials: K
authors.lastname: Hofmann
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.forename: Huib
authors.initials: H
authors.lastname: Ovaa
authors.forename: Joachim
authors.initials: J
authors.lastname: Wittbrodt
authors.forename: Erik
authors.initials: E
authors.lastname: Meulmeester
authors.forename: Frauke
authors.initials: F
authors.lastname: Melchior
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D020541:Coiled Bodies / Q000378:metabolism; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D029961:Zebrafish Proteins; C068921:p80-coilin; D010450:Endopeptidases; C000592698:USPL1 protein, human; D064570:Ubiquitin-Specific Proteases; C579189:USPL1 protein, zebrafish; C091939:ubiquitin isopeptidase