| First Author | Liu S | Year | 2018 |
| Journal | Nat Immunol | Volume | 19 |
| Issue | 1 | Pages | 41-52 |
| PubMed ID | 29242538 | Mgi Jnum | J:282658 |
| Mgi Id | MGI:6381310 | Doi | 10.1038/s41590-017-0003-0 |
| Citation | Liu S, et al. (2018) Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA. Nat Immunol 19(1):41-52 |
| abstractText | Prolonged activation of interferon-STAT1 signaling is closely related to inflammatory autoimmune disorders, and therefore the identification of negative regulators of these pathways is important. Through high-content screening of 115 mouse RING-domain E3 ligases, we identified the E3 ubiquitin ligase RNF2 as a potent inhibitor of interferon-dependent antiviral responses. RNF2 deficiency substantially enhanced interferon-stimulated gene (ISG) expression and antiviral responses. Mechanistically, nuclear RNF2 directly bound to STAT1 after interferon stimulation and increased K33-linked polyubiquitination of the DNA-binding domain of STAT1 at position K379, in addition to promoting the disassociation of STAT1/STAT2 from DNA and consequently suppressing ISG transcription. Our study provides insight into the regulation of interferon-dependent responses via a previously unrecognized post-translational modification of STAT1 in the nucleus. |
