| First Author | Xia X | Year | 2011 |
| Journal | Immunity | Volume | 34 |
| Issue | 6 | Pages | 843-53 |
| PubMed ID | 21703539 | Mgi Jnum | J:173996 |
| Mgi Id | MGI:5050762 | Doi | 10.1016/j.immuni.2011.02.022 |
| Citation | Xia X, et al. (2011) NLRX1 Negatively Regulates TLR-Induced NF-kappaB Signaling by Targeting TRAF6 and IKK. Immunity 34(6):843-53 |
| abstractText | Tight regulation of NF-kappaB signaling is essential for innate and adaptive immune responses, yet the molecular mechanisms responsible for its negative regulation are not completely understood. Here, we report that NLRX1, a NOD-like receptor family member, negatively regulates Toll-like receptor-mediated NF-kappaB activation. NLRX1 interacts with TRAF6 or IkappaB kinase (IKK) in an activation signal-dependent fashion. Upon LPS stimulation, NLRX1 is rapidly ubiquitinated, disassociates from TRAF6, and then binds to the IKK complex, resulting in inhibition of IKKalpha and IKKbeta phosphorylation and NF-kappaB activation. Knockdown of NLRX1 in various cell types markedly enhances IKK phosphorylation and the production of NF-kappaB-responsive cytokines after LPS stimulation. We further provide in vivo evidence that NLRX1 knockdown in mice markedly enhances susceptibility to LPS-induced septic shock and plasma IL-6 level. Our study identifies a previously unrecognized role for NLRX1 in the negative regulation of TLR-induced NF-kappaB activation by dynamically interacting with TRAF6 and the IKK complex. |
