| First Author | Hao Q | Year | 2015 |
| Journal | EMBO J | Volume | 34 |
| Issue | 23 | Pages | 2903-20 |
| PubMed ID | 26471729 | Mgi Jnum | J:227762 |
| Mgi Id | MGI:5702782 | Doi | 10.15252/embj.201591888 |
| Citation | Hao Q, et al. (2015) A non-canonical role of the p97 complex in RIG-I antiviral signaling. EMBO J 34(23):2903-20 |
| abstractText | RIG-I is a well-studied sensor of viral RNA that plays a key role in innate immunity. p97 regulates a variety of cellular events such as protein quality control, membrane reassembly, DNA repair, and the cell cycle. Here, we report a new role for p97 with Npl4-Ufd1 as its cofactor in reducing antiviral innate immune responses by facilitating proteasomal degradation of RIG-I. The p97 complex is able to directly bind both non-ubiquitinated RIG-I and the E3 ligase RNF125, promoting K48-linked ubiquitination of RIG-I at residue K181. Viral infection significantly strengthens the interaction between RIG-I and the p97 complex by a conformational change of RIG-I that exposes the CARDs and through K63-linked ubiquitination of these CARDs. Disruption of the p97 complex enhances RIG-I antiviral signaling. Consistently, administration of compounds targeting p97 ATPase activity was shown to inhibit viral replication and protect mice from vesicular stomatitis virus (VSV) infection. Overall, our study uncovered a previously unrecognized role for the p97 complex in protein ubiquitination and revealed the p97 complex as a potential drug target in antiviral therapy. |
