• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

NLRX1 negatively regulates TLR-induced NF-κB signaling by targeting TRAF6 and IKK.

Tight regulation of NF-κB 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-κB activation. NLRX1 interacts with TRAF6 or IκB 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 IKKα and IKKβ phosphorylation and NF-κB activation. Knockdown of NLRX1 in various cell types markedly enhances IKK phosphorylation and the production of NF-κB-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-κB activation by dynamically interacting with TRAF6 and the IKK complex.

Pubmed ID: 21703539

Authors

  • Xia X
  • Cui J
  • Wang HY
  • Zhu L
  • Matsueda S
  • Wang Q
  • Yang X
  • Hong J
  • Songyang Z
  • Chen ZJ
  • Wang RF

Journal

Immunity

Publication Data

June 24, 2011

Associated Grants

  • Agency: NCI NIH HHS, Id: P01 CA094237
  • Agency: NCI NIH HHS, Id: P01 CA094237-10
  • Agency: NCI NIH HHS, Id: P50 CA126752
  • Agency: NCI NIH HHS, Id: P50 CA126752-05
  • Agency: NCI NIH HHS, Id: R01 CA090327
  • Agency: NCI NIH HHS, Id: R01 CA090327-09
  • Agency: NCI NIH HHS, Id: R01 CA101795
  • Agency: NCI NIH HHS, Id: R01 CA101795-05
  • Agency: NCI NIH HHS, Id: R01 CA116408
  • Agency: NCI NIH HHS, Id: R01 CA116408-05
  • Agency: NCI NIH HHS, Id: R01 CA121191
  • Agency: NCI NIH HHS, Id: R01 CA121191-05

Mesh Terms

  • Animals
  • Cell Line
  • Cytokines
  • Humans
  • I-kappa B Kinase
  • Lipopolysaccharides
  • Mice
  • Mitochondrial Proteins
  • NF-kappa B
  • Phosphorylation
  • Protein Binding
  • Signal Transduction
  • TNF Receptor-Associated Factor 6
  • Toll-Like Receptors
  • Ubiquitination