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

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  • dc.contributor.author Santos-Barriopedro, Irene
  • dc.contributor.author Bosch-Presegué, Laia
  • dc.contributor.author Marazuela-Duque, Anna
  • dc.contributor.author Torre, Carolina de la
  • dc.contributor.author Colomer Montañà, Carlota, 1990-
  • dc.contributor.author Vázquez, Berta N.
  • dc.contributor.author Fuhrmann, Thomas
  • dc.contributor.author Martínez-Pastor, Bárbara
  • dc.contributor.author Lu, Wenfu
  • dc.contributor.author Braun, Thomas
  • dc.contributor.author Bober, Eva
  • dc.contributor.author Jenuwein, Thomas
  • dc.contributor.author Serrano, Lourdes
  • dc.contributor.author Esteller, Manel
  • dc.contributor.author Chen, Zhenbang
  • dc.contributor.author Barceló-Batllori, Silvia
  • dc.contributor.author Mostoslavsky, Raúl
  • dc.contributor.author Espinosa Blay, Lluís
  • dc.contributor.author Vaquero, Alejandro
  • dc.date.accessioned 2018-12-12T08:34:12Z
  • dc.date.available 2018-12-12T08:34:12Z
  • dc.date.issued 2018
  • dc.description.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.
  • dc.description.sponsorship This work was supported by the Fundació La Marató de TV3 (20133810 to A.V.), the Spanish Ministry of Economy and competitiveness-MINECO (SAF2011-25860, SAF2014-55964R to A.V.) confunded by FEDER funds/European Regional Development Fund (ERDF)-a way to Build Europe, and the Catalan government agency AGAUR (2009-SGR-914 to A.V.) The IDIBELL Proteomics Unit belongs to ProteoRed, PRB2-ISCIII, and is supported by grant PT13/0001/0033 and Cellex Foundation. S.B.B. is the recipient of a 13FIS037 fellowship.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Santos-Barriopedro I, Bosch-Presegué L, Marazuela-Duque A, de la Torre C, Colomer C, Vazquez BN. Et al. SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-κB pathway. Nat Commun. 2018 Jan 9;9(1):101. DOI: 10.1038/s41467-017-02586-x
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-017-02586-x
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/36037
  • dc.language.iso eng
  • dc.publisher Nature Publishing Group
  • dc.relation.ispartof Nature Communications. 2018 Jan 9;9(1):101
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-25860
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-55964R
  • dc.rights This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Plasticitat fenotípica
  • dc.subject.other Estrès -- Aspectes fisiològics
  • dc.title SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-κB pathway
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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