2026-06-14T03:43:11Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/262202025-12-18T12:55:51Zcom_20.500.12105_2273com_20.500.12105_2202col_20.500.12105_19571

00925njm 22002777a 4500 dc Santos-Barriopedro, Irene author Bosch-Presegué, Laia author Marazuela-Duque, Anna author de la Torre, Carolina author Colomer, Carlota author Vazquez, Berta N author Fuhrmann, Thomas author Martínez-Pastor, Bárbara author Lu, Wenfu author Braun, Thomas author Bober, Eva author Jenuwein, Thomas author Serrano, Lourdes author Esteller, Manel author Chen, Zhenbang author Barceló-Batllori, Silvia author Mostoslavsky, Raúl author Espinosa, Lluis author Vaquero, Alejandro author 2018-01-09 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. Nat Commun . 2018 Jan 9;9(1):101 Nature Communications 29317652 https://hdl.handle.net/20.500.12105/26220 SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-κB pathway.