title: Characterization of SENP7, a SUMO-2/3-specific isopeptidase.
abstract: The modification of proteins by SUMO (small ubiquitin-related modifier) plays important roles in regulating the activity, stability and cellular localization of target proteins. Similar to ubiquitination, SUMO modification is a dynamic process that can be reversed by SENPs [SUMO-1/sentrin/SMT3 (suppressor of mif two 3 homologue 1)-specific peptidases]. To date, six SENPs have been discovered in humans, although knowledge of their regulation, specificity and biological functions is limited. In the present study, we report that SENP7 has a restricted substrate specificity, being unable to process SUMO precursors and displaying paralogue-specific isopeptidase activity. The C-terminal catalytic domain of SENP7 efficiently depolymerized poly-SUMO-2 chains but had undetectable activity against poly-SUMO-1 chains. SENP7 also displayed isopeptidase activity against di-SUMO-2- and SUMO-2-modified RanGAP1 (Ran GTPase-activating protein 1) but had limited activity against SUMO-1-modified RanGAP1. in vivo, full-length SENP7 was localized to the nucleoplasm and preferentially reduced the accumulation of high-molecular-mass conjugates of SUMO-2 and SUMO-3 compared with SUMO-1. Small interfering RNA-mediated ablation of SENP7 expression led to the accumulation of high-molecular-mass SUMO-2 species and to the accumulation of promyelocytic leukaemia protein in subnuclear bodies. These findings suggest that SENP7 acts as a SUMO-2/3-specific protease that is likely to regulate the metabolism of poly-SUMO-2/3 rather than SUMO-1 conjugation in vivo.
authors.affiliation: Wellcome Trust Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dow Street, Dundee DD15EH, Scotland, UK.
authors.forename: Lin Nan
authors.initials: LN
authors.lastname: Shen
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Geoffroy
authors.forename: Ellis G
authors.initials: EG
authors.lastname: Jaffray
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Hay
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D019759:Carbon-Nitrogen Lyases / Q000737:chemistry* / Q000378:metabolism; D002522:Chlorocebus aethiops; D010450:Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D025841:Small Ubiquitin-Related Modifier Proteins / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D014162:Transfection
chemical_list: D020690:GTPase-Activating Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D010450:Endopeptidases; C533959:SENP7 protein, human; D019759:Carbon-Nitrogen Lyases; C034300:isopeptidase