Santos-Barriopedro, IreneBosch-Presegué, LaiaMarazuela-Duque, AnnaTorre, Carolina de laColomer Montañà, Carlota, 1990-Vázquez, Berta N.Fuhrmann, ThomasMartínez-Pastor, BárbaraLu, WenfuBraun, ThomasBober, EvaJenuwein, ThomasSerrano, LourdesEsteller, ManelChen, ZhenbangBarceló-Batllori, SilviaMostoslavsky, RaúlEspinosa Blay, LluísVaquero, Alejandro2018-12-122018-12-122018Santos-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-x2041-1723http://hdl.handle.net/10230/36037Sirtuins 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.application/pdfengThis 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/.Plasticitat fenotípicaEstrès -- Aspectes fisiològicsinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-017-02586-xinfo:eu-repo/semantics/openAccess