Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125.
Retinoic acid-inducible gene I (RIG-I) plays a pivotal role in the regulation of cytokine production induced by pathogens. The RIG-I also augments the production of IFN and other cytokines via an amplification circuit. Because the production of cytokines is closely controlled, up- and down-regulation of RIG-I signaling also needs strict ... regulation. The mechanism of this regulation, however, remains elusive. Here, we found that RIG-I undergoes proteasomal degradation after conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5, a family protein of RIG-I as well as IPS-1, which is also a downstream protein of RIG-I signaling that results in suppressing the functions of these proteins. Because RNF125 is enhanced by IFN, these functions constitute a negative regulatory loop circuit for IFN production.
Mesh Terms:
Animals, DEAD-box RNA Helicases, Gene Expression Regulation, Humans, Interferon Regulatory Factor-3, Interferon-alpha, Mice, Poly I-C, Protein Binding, Signal Transduction, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
Animals, DEAD-box RNA Helicases, Gene Expression Regulation, Humans, Interferon Regulatory Factor-3, Interferon-alpha, Mice, Poly I-C, Protein Binding, Signal Transduction, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
Proc Natl Acad Sci U S A
Date: May. 01, 2007
PubMed ID: 17460044
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