The SUMO protease SENP6 is a direct regulator of PML nuclear bodies

Neil Hattersley, Linnan Shen, Ellis G. Jaffray, Ronald T. Hay

    Research output: Contribution to journalArticle

    35 Citations (Scopus)

    Abstract

    Promyelocytic leukemia protein (PML) is the core component of PML-nuclear bodies (PML NBs). The small ubiquitin-like modifier (SUMO) system (and, in particular, SUMOylation of PML) is a critical component in the formation and regulation of PML NBs. SUMO protease SENP6 has been shown previously to be specific for SUMO-2/3-modified substrates and shows preference for SUMO polymers. Here, we further investigate the substrate specificity of SENP6 and show that it is also capable of cleaving mixed chains of SUMO-1 and SUMO-2/3. Depletion of SENP6 results in accumulation of endogenous SUMO-2/3 and SUMO-1 conjugates, and immunofluorescence analysis shows accumulation of SUMO and PML in an increased number of PML NBs. Although SENP6 depletion drastically increases the size of PML NBs, the organizational structure of the body is not affected. Mutation of the catalytic cysteine of SENP6 results in its accumulation in PML NBs, and biochemical analysis indicates that SUMO-modified PML is a substrate of SENP6.

    Original languageEnglish
    Pages (from-to)78-90
    Number of pages13
    JournalMolecular Biology of the Cell
    Volume22
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2011

    Keywords

    • ACUTE PROMYELOCYTIC LEUKEMIA
    • STRUCTURAL BASIS
    • CELL-PROLIFERATION
    • BODY FORMATION
    • BINDING MOTIF
    • RAR-ALPHA
    • LOCALIZATION
    • CONJUGATION
    • PATHWAY
    • IDENTIFICATION

    Cite this

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    title = "The SUMO protease SENP6 is a direct regulator of PML nuclear bodies",
    abstract = "Promyelocytic leukemia protein (PML) is the core component of PML-nuclear bodies (PML NBs). The small ubiquitin-like modifier (SUMO) system (and, in particular, SUMOylation of PML) is a critical component in the formation and regulation of PML NBs. SUMO protease SENP6 has been shown previously to be specific for SUMO-2/3-modified substrates and shows preference for SUMO polymers. Here, we further investigate the substrate specificity of SENP6 and show that it is also capable of cleaving mixed chains of SUMO-1 and SUMO-2/3. Depletion of SENP6 results in accumulation of endogenous SUMO-2/3 and SUMO-1 conjugates, and immunofluorescence analysis shows accumulation of SUMO and PML in an increased number of PML NBs. Although SENP6 depletion drastically increases the size of PML NBs, the organizational structure of the body is not affected. Mutation of the catalytic cysteine of SENP6 results in its accumulation in PML NBs, and biochemical analysis indicates that SUMO-modified PML is a substrate of SENP6.",
    keywords = "ACUTE PROMYELOCYTIC LEUKEMIA, STRUCTURAL BASIS, CELL-PROLIFERATION, BODY FORMATION, BINDING MOTIF, RAR-ALPHA, LOCALIZATION, CONJUGATION, PATHWAY, IDENTIFICATION",
    author = "Neil Hattersley and Linnan Shen and Jaffray, {Ellis G.} and Hay, {Ronald T.}",
    year = "2011",
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    The SUMO protease SENP6 is a direct regulator of PML nuclear bodies. / Hattersley, Neil; Shen, Linnan; Jaffray, Ellis G.; Hay, Ronald T.

    In: Molecular Biology of the Cell, Vol. 22, No. 1, 01.01.2011, p. 78-90.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The SUMO protease SENP6 is a direct regulator of PML nuclear bodies

    AU - Hattersley, Neil

    AU - Shen, Linnan

    AU - Jaffray, Ellis G.

    AU - Hay, Ronald T.

    PY - 2011/1/1

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    N2 - Promyelocytic leukemia protein (PML) is the core component of PML-nuclear bodies (PML NBs). The small ubiquitin-like modifier (SUMO) system (and, in particular, SUMOylation of PML) is a critical component in the formation and regulation of PML NBs. SUMO protease SENP6 has been shown previously to be specific for SUMO-2/3-modified substrates and shows preference for SUMO polymers. Here, we further investigate the substrate specificity of SENP6 and show that it is also capable of cleaving mixed chains of SUMO-1 and SUMO-2/3. Depletion of SENP6 results in accumulation of endogenous SUMO-2/3 and SUMO-1 conjugates, and immunofluorescence analysis shows accumulation of SUMO and PML in an increased number of PML NBs. Although SENP6 depletion drastically increases the size of PML NBs, the organizational structure of the body is not affected. Mutation of the catalytic cysteine of SENP6 results in its accumulation in PML NBs, and biochemical analysis indicates that SUMO-modified PML is a substrate of SENP6.

    AB - Promyelocytic leukemia protein (PML) is the core component of PML-nuclear bodies (PML NBs). The small ubiquitin-like modifier (SUMO) system (and, in particular, SUMOylation of PML) is a critical component in the formation and regulation of PML NBs. SUMO protease SENP6 has been shown previously to be specific for SUMO-2/3-modified substrates and shows preference for SUMO polymers. Here, we further investigate the substrate specificity of SENP6 and show that it is also capable of cleaving mixed chains of SUMO-1 and SUMO-2/3. Depletion of SENP6 results in accumulation of endogenous SUMO-2/3 and SUMO-1 conjugates, and immunofluorescence analysis shows accumulation of SUMO and PML in an increased number of PML NBs. Although SENP6 depletion drastically increases the size of PML NBs, the organizational structure of the body is not affected. Mutation of the catalytic cysteine of SENP6 results in its accumulation in PML NBs, and biochemical analysis indicates that SUMO-modified PML is a substrate of SENP6.

    KW - ACUTE PROMYELOCYTIC LEUKEMIA

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    KW - CELL-PROLIFERATION

    KW - BODY FORMATION

    KW - BINDING MOTIF

    KW - RAR-ALPHA

    KW - LOCALIZATION

    KW - CONJUGATION

    KW - PATHWAY

    KW - IDENTIFICATION

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