| First Author | Cui J | Year | 2010 |
| Journal | Cell | Volume | 141 |
| Issue | 3 | Pages | 483-96 |
| PubMed ID | 20434986 | Mgi Jnum | J:160362 |
| Mgi Id | MGI:4454346 | Doi | 10.1016/j.cell.2010.03.040 |
| Citation | Cui J, et al. (2010) NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways. Cell 141(3):483-96 |
| abstractText | Stringent control of the NF-kappaB and type I interferon signaling pathways is critical to effective host immune responses, yet the molecular mechanisms that negatively regulate these pathways are poorly understood. Here, we show that NLRC5, a member of the highly conserved NOD-like protein family, can inhibit the IKK complex and RIG-I/MDA5 function. NLRC5 inhibited NF-kappaB-dependent responses by interacting with IKKalpha and IKKbeta and blocking their phosphorylation. It also interacted with RIG-I and MDA5, but not with MAVS, to inhibit RLR-mediated type I interferon responses. Consistent with these observations, NLRC5-specific siRNA knockdown not only enhanced the activation of NF-kappaB and its responsive genes, TNF-alpha and IL-6, but also promoted type I interferon signaling and antiviral immunity. Our findings identify NLRC5 as a negative regulator that blocks two central components of the NF-kappaB and type I interferon signaling pathways and suggest an important role for NLRC5 in homeostatic control of innate immunity. |
