Characterization of SENP7, a SUMO-2/3-specific isopeptidase

Lin Nan Shen, Marie-Claude Geoffroy, Ellis G. Jaffray, Ronald T. Hay

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    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.

    Original languageEnglish
    Pages (from-to)223-230
    Number of pages8
    JournalBiochemical Journal
    Volume421
    DOIs
    Publication statusPublished - 15 Jul 2009

    Keywords

    • conjugation
    • deconjugation
    • isopeptidase
    • small ubiquitin-related modifier(SUMO)
    • SUMO-1/sentrin/SMT3-specific peptidase 7 (SENP7)
    • ubiquitin
    • HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEINS
    • SUMO MODIFICATION
    • PORE COMPLEX
    • PROTEINS
    • PROTEASE
    • YEAST
    • IDENTIFICATION
    • CONJUGATION
    • PML
    • SUMOYLATION

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