Abstract

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.

Keywords

Ubiquitin ligaseUbiquitinRIG-ICell biologyBiologyUbiquitin-conjugating enzymeMDA5CytokineSignal transductionGeneRNABiochemistryGeneticsRNA interference

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Year
2007
Type
article
Volume
104
Issue
18
Pages
7500-7505
Citations
450
Access
Closed

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Kei‐ichiro Arimoto, Hitoshi Takahashi, Takayuki Hishiki et al. (2007). Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proceedings of the National Academy of Sciences , 104 (18) , 7500-7505. https://doi.org/10.1073/pnas.0611551104

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DOI
10.1073/pnas.0611551104