SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-κB pathway
Year: 2018
Type: article
Abstract: -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.
Source: Nature Communications
Authors: 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, Eva Bober, Thomas Jenuwein, Lourdes Serrano, Manel Esteller, Zhenbang Chen, Silvia Barceló-Batllori, Raúl Mostoslavsky, Lluis Espinosa, Alejandro Vaquero
Institutions: Institut d'Investigació Biomédica de Bellvitge, Universitat de Vic - Universitat Central de Catalunya, Barcelona Biomedical Research Park, Municipal Institute for Medical Research, Hospital del Mar Research Institute, Rutgers, The State University of New Jersey, Max Planck Institute of Immunobiology and Epigenetics, Harvard University, Massachusetts General Hospital, Meharry Medical College, Max Planck Institute for Heart and Lung Research, Institució Catalana de Recerca i Estudis Avançats, Universitat de Barcelona
Language: English
Topic: NF-κB Signaling Pathways
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Dana-Farber Cancer Institute, Fundación Cellex, Fundació la Marató de TV3, Ministerio de Economía y Competitividad, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, European Regional Development Fund, National Cancer Institute, National Institute on Minority Health and Health Disparities
OpenAlex ID: W2781979842