NLRC5 Negatively regulates the NF-κB and type I interferon signaling pathways

Jun Cui, Liang Zhu, Xiaojun Xia, Helen Y. Wang, Xavier Legras, Jun Hong, Jiabing Ji, Pingping Shen, Shu Zheng, Zhijian J. Chen, Rong Fu Wang

Research output: Contribution to journalArticle

230 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)483-496
Number of pages14
JournalCell
Volume141
Issue number3
DOIs
StatePublished - Apr 2010

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Interferon Type I
Phosphorylation
Critical Pathways
Innate Immunity
Small Interfering RNA
Antiviral Agents
Immunity
Interleukin-6
Genes
Chemical activation
Proteins

Keywords

  • Cellimmuno
  • Molimmuno
  • Signaling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cui, J., Zhu, L., Xia, X., Wang, H. Y., Legras, X., Hong, J., ... Wang, R. F. (2010). NLRC5 Negatively regulates the NF-κB and type I interferon signaling pathways. Cell, 141(3), 483-496. https://doi.org/10.1016/j.cell.2010.03.040

NLRC5 Negatively regulates the NF-κB and type I interferon signaling pathways. / Cui, Jun; Zhu, Liang; Xia, Xiaojun; Wang, Helen Y.; Legras, Xavier; Hong, Jun; Ji, Jiabing; Shen, Pingping; Zheng, Shu; Chen, Zhijian J.; Wang, Rong Fu.

In: Cell, Vol. 141, No. 3, 04.2010, p. 483-496.

Research output: Contribution to journalArticle

Cui, J, Zhu, L, Xia, X, Wang, HY, Legras, X, Hong, J, Ji, J, Shen, P, Zheng, S, Chen, ZJ & Wang, RF 2010, 'NLRC5 Negatively regulates the NF-κB and type I interferon signaling pathways', Cell, vol. 141, no. 3, pp. 483-496. https://doi.org/10.1016/j.cell.2010.03.040
Cui J, Zhu L, Xia X, Wang HY, Legras X, Hong J et al. NLRC5 Negatively regulates the NF-κB and type I interferon signaling pathways. Cell. 2010 Apr;141(3):483-496. https://doi.org/10.1016/j.cell.2010.03.040
Cui, Jun ; Zhu, Liang ; Xia, Xiaojun ; Wang, Helen Y. ; Legras, Xavier ; Hong, Jun ; Ji, Jiabing ; Shen, Pingping ; Zheng, Shu ; Chen, Zhijian J. ; Wang, Rong Fu. / NLRC5 Negatively regulates the NF-κB and type I interferon signaling pathways. In: Cell. 2010 ; Vol. 141, No. 3. pp. 483-496.
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