Title: Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. | Journal: Proceedings of the National Academy of Sciences of the United States of America. 2007 May;104(18):7500-5 | Authors: Arimoto K, Takahashi H, Hishiki T, Konishi H, Fujita T, Shimotohno K. | 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. | See full PubMed entry: http://www.ncbi.nlm.nih.gov/pubmed/17460044 |
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