期刊
CELL
卷 141, 期 3, 页码 483-496出版社
CELL PRESS
DOI: 10.1016/j.cell.2010.03.040
关键词
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资金
- National Cancer Institute [P01CA094237, P50CA126752, R01CA09327, R01CA101795, R01CA116408, R01CA121191]
- NIH
- Cancer Research Institute
- China Scholarship Council
- [NCET-06-0445]
Stringent control of the NF-kappa B 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-kappa B-dependent responses by interacting with IKK alpha and IKK beta 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-kappa B 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-kappa B and type I interferon signaling pathways and suggest an important role for NLRC5 in homeostatic control of innate immunity.
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