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SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-κB pathway

Author

Listed:
  • Irene Santos-Barriopedro

    (Bellvitge Biomedical Research Institute (IDIBELL))

  • Laia Bosch-Presegué

    (Bellvitge Biomedical Research Institute (IDIBELL)
    Universitat de Vic, Universitat Central de Catalunya)

  • Anna Marazuela-Duque

    (Bellvitge Biomedical Research Institute (IDIBELL))

  • Carolina de la Torre

    (Bellvitge Biomedical Research Institute (IDIBELL))

  • Carlota Colomer

    (IMIM-Hospital del Mar, Barcelona Biomedical Research Park (PRBB))

  • Berta N. Vazquez

    (The State University of New Jersey)

  • Thomas Fuhrmann

    (Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51)

  • Bárbara Martínez-Pastor

    (Harvard Medical School)

  • Wenfu Lu

    (Meharry Medical College)

  • Thomas Braun

    (Max-Planck-Institute for Heart and Lung Research)

  • Eva Bober

    (Max-Planck-Institute for Heart and Lung Research)

  • Thomas Jenuwein

    (Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51)

  • Lourdes Serrano

    (The State University of New Jersey)

  • Manel Esteller

    (Bellvitge Biomedical Research Institute (IDIBELL)
    School of Medicine, University of Barcelona
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

  • Zhenbang Chen

    (Meharry Medical College)

  • Silvia Barceló-Batllori

    (Bellvitge Biomedical Research Institute (IDIBELL))

  • Raúl Mostoslavsky

    (Harvard Medical School)

  • Lluis Espinosa

    (IMIM-Hospital del Mar, Barcelona Biomedical Research Park (PRBB))

  • Alejandro Vaquero

    (Bellvitge Biomedical Research Institute (IDIBELL))

Abstract

Sirtuins are NAD+-dependent deacetylases that facilitate cellular stress response. They include SirT6, which protects genome stability and regulates metabolic homeostasis through gene silencing, and whose loss induces an accelerated aging phenotype directly linked to hyperactivation of the NF-κB pathway. Here we show that SirT6 binds to the H3K9me3-specific histone methyltransferase Suv39h1 and induces monoubiquitination of conserved cysteines in the PRE-SET domain of Suv39h1. Following activation of NF-κB signaling Suv39h1 is released from the IκBα locus, subsequently repressing the NF-κB pathway. We propose that SirT6 attenuates the NF-κB pathway through IκBα upregulation via cysteine monoubiquitination and chromatin eviction of Suv39h1. We suggest a mechanism based on SirT6-mediated enhancement of a negative feedback loop that restricts the NF-κB pathway.

Suggested Citation

  • Irene Santos-Barriopedro & Laia Bosch-Presegué & Anna Marazuela-Duque & Carolina de la Torre & Carlota Colomer & Berta N. Vazquez & Thomas Fuhrmann & Bárbara Martínez-Pastor & Wenfu Lu & Thomas Braun , 2018. "SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-κB pathway," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02586-x
    DOI: 10.1038/s41467-017-02586-x
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