| First Author | Santos-Barriopedro I | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 101 |
| PubMed ID | 29317652 | Mgi Jnum | J:257727 |
| Mgi Id | MGI:6114935 | Doi | 10.1038/s41467-017-02586-x |
| Citation | Santos-Barriopedro I, et al. (2018) SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-kappaB pathway. Nat Commun 9(1):101 |
| abstractText | 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-kappaB 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-kappaB signaling Suv39h1 is released from the IkappaBalpha locus, subsequently repressing the NF-kappaB pathway. We propose that SirT6 attenuates the NF-kappaB pathway through IkappaBalpha 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-kappaB pathway. |
