| First Author | Zhou P | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 1243 |
| PubMed ID | 29593341 | Mgi Jnum | J:260756 |
| Mgi Id | MGI:6149354 | Doi | 10.1038/s41467-018-03563-8 |
| Citation | Zhou P, et al. (2018) MLL5 suppresses antiviral innate immune response by facilitating STUB1-mediated RIG-I degradation. Nat Commun 9(1):1243 |
| abstractText | Trithorax group protein MLL5 is an important epigenetic modifier that controls cell cycle progression, chromatin architecture maintenance, and hematopoiesis. However, whether MLL5 has a role in innate antiviral immunity is largely unknown. Here we show that MLL5 suppresses the RIG-I-mediated anti-viral immune response. Mll5-deficient mice infected with vesicular stomatitis virus show enhanced anti-viral innate immunity, reduced morbidity, and viral load. Mechanistically, a fraction of MLL5 located in the cytoplasm interacts with both RIG-I and its E3 ubiquitin ligase STUB1, which promotes K48-linked polyubiquitination and proteasomal degradation of RIG-I. MLL5 deficiency attenuates the RIG-I and STUB1 association, reducing K48-linked polyubiquitination and accumulation of RIG-I protein in cells. Upon virus infection, nuclear MLL5 protein translocates from the nucleus to the cytoplasm inducing STUB1-mediated degradation of RIG-I. Our study uncovers a previously unrecognized role for MLL5 in antiviral innate immune responses and suggests a new target for controlling viral infection. |
