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NLRC5 Negatively Regulates the NF-κB and Type I Interferon Signaling Pathways
- Source :
-
Cell . Apr2010, Vol. 141 Issue 3, p483-496. 14p. - Publication Year :
- 2010
-
Abstract
- Summary: Stringent control of the NF-κB 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-κB-dependent responses by interacting with IKKα and IKKβ 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-κB and its responsive genes, TNF-α 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-κB and type I interferon signaling pathways and suggest an important role for NLRC5 in homeostatic control of innate immunity. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00928674
- Volume :
- 141
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 58637972
- Full Text :
- https://doi.org/10.1016/j.cell.2010.03.040