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

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 pat...

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Bibliographic Details
Authors: Santos Barriopedro, Irene, Bosch Presegué, Laia, Marazuela Duque, Anna, Torre Gómez, Carolina de la, Colomer, Carlota, Vàzquez Prat, Berta N., Fuhrmann, Thomas, Martínez-Pastor, Bárbara, Lu, Wenfu, Braun, Thomas, Bober, Eva, Jenuwein, Thomas, Serrano, Lourdes, Esteller, Manel, Cheng, Zhenbang, Barceló-Batllori, Sílvia, Mostoslavsky, Raúl, Espinosa, Lluís, Vaquero García, Alejandro
Format: article
Status:Published version
Publication Date:2018
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/120949
Online Access:https://hdl.handle.net/2445/120949
Access Level:Open access
Keyword:Cromatina
Epigenètica
Histones
Chromatin
Epigenetics
Description
Summary: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.

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