Phosphorylation of serine 303 is a prerequisite for the stress-inducible SUMO modification of heat shock factor 1

V Hietakangas, JK Ahlskog, AM Jakobsson, M Hellesuo, NM Sahlberg, CI Holmberg, A Mikhailov, JJ Palvimo, L Pirkkala, Lea Sistonen

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    Abstrakti

    The heat shock response, which is accompanied by a rapid and robust upregulation of heat shock proteins (Hsps), is a highly conserved protection mechanism against protein-damaging stress. Hsp induction is mainly regulated at transcriptional level by stress-inducible heat shock factor 1 (HSF1). Upon activation, HSF1 trimerizes, binds to DNA, concentrates in the nuclear stress granules, and undergoes a marked multisite phosphorylation, which correlates with its transcriptional activity. In this study, we show that HSF1 is modified by SUMO-1 and SUMO-2 in a stress-inducible manner. Sumoylation is rapidly and transiently enhanced on lysine 298, located in the regulatory domain of HSF1, adjacent to several critical phosphorylation sites. Sumoylation analyses of HSF1 phosphorylation site mutants reveal that specifically the phosphorylation-deficient S303 mutant remains devoid of SUMO modification in vivo and the mutant mimicking phosphorylation of S303 promotes HSF1 sumoylation in vitro, indicating that S303 phospborylation is required for K298 sumoylation. This finding is further supported by phosphopeptide mapping and analysis with S303/7 phosphospecific antibodies, which demonstrate that serine 303 is a target for strong heat-inducible phosphorylation, corresponding to the inducible HSF1 sumoylation. A transient phosphorylation-dependent colocalization of HSF1 and SUMO-1 in nuclear stress granules provides evidence for a strictly regulated subnuclear interplay between HSF1 and SUMO.
    AlkuperäiskieliEi tiedossa
    Sivut2953–2968
    Sivumäärä16
    JulkaisuMolecular and Cellular Biology
    Vuosikerta23
    Numero8
    DOI - pysyväislinkit
    TilaJulkaistu - 2003
    OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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