| First Author | Chen ST | Year | 2019 |
| Journal | Cell Host Microbe | Volume | 25 |
| Issue | 4 | Pages | 602-616.e7 |
| PubMed ID | 30902577 | Mgi Jnum | J:293592 |
| Mgi Id | MGI:6443016 | Doi | 10.1016/j.chom.2019.02.013 |
| Citation | Chen ST, et al. (2019) NLRP12 Regulates Anti-viral RIG-I Activation via Interaction with TRIM25. Cell Host Microbe 25(4):602-616.e7 |
| abstractText | Establishing the balance between positive and negative innate immune mechanisms is crucial for maintaining homeostasis. Here we uncover the regulatory crosstalk between two previously unlinked innate immune receptor families: RIG-I, an anti-viral cytosolic receptor activated type I interferon production, and NLR (nucleotide-binding domain, leucine repeat domain-containing protein). We show that NLRP12 dampens RIG-I-mediated immune signaling against RNA viruses by controlling RIG-I's association with its adaptor MAVS. The nucleotide-binding domain of NLRP12 interacts with the ubiquitin ligase TRIM25 to prevent TRIM25-mediated, Lys63-linked ubiquitination and activation of RIG-I. NLRP12 also enhances RNF125-mediated, Lys48-linked degradative ubiquitination of RIG-I. Vesicular stomatitis virus (VSV) infection downregulates NLRP12 expression to allow RIG-I activation. Myeloid-cell-specific Nlrp12-deficient mice display a heightened interferon and TNF response and are more resistant to VSV infection. These results indicate that NLRP12 functions as a checkpoint for anti-viral RIG-I activation. |
