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

Santos-Barriopedro, I., Bosch-Presegue, L., Marazuela-Duque, A., de la Torre, C., Colomer, C., Vazquez, B. N., et al. (2018). SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-kappa B pathway. NATURE COMMUNICATIONS, 9, 101. doi:10.1038/s41467-017-02586-x.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-C235-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-C236-3
Genre: Journal Article

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Santos-Barriopedro, Irene, Author
Bosch-Presegue, Laia, Author
Marazuela-Duque, Anna, Author
de la Torre, Carolina, Author
Colomer, Carlota, Author
Vazquez, Berta N., Author
Fuhrmann, Thomas, Author
Martinez-Pastor, Barbara, Author
Lu, Wenfu, Author
Braun, Thomas1, Author              
Bober, Eva1, Author              
Jenuwein, Thomas2, Author              
Serrano, Lourdes, Author
Esteller, Manel, Author
Chen, Zhenbang, Author
Barcelo-Batllori, Silvia, Author
Mostoslavsky, Raul, Author
Espinosa, Lluis, Author
Vaquero, Alejandro, Author
Affiliations:
1Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              
2Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644              

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 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.

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Language(s): eng - English
 Dates: 20182018
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-017-02586-x
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Title: NATURE COMMUNICATIONS
Source Genre: Journal
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Pages: - Volume / Issue: 9 Sequence Number: - Start / End Page: 101 Identifier: ISSN: 2041-1723