期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 18, 页码 7500-7505出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0611551104
关键词
innate immunity; signal transduction
Retinoic acid-inducible gene I (RIG-1) plays a pivotal role in the regulation of cytokine production induced by pathogens. The RIG-1 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-1 signaling also needs strict regulation. The mechanism of this regulation, however, remains elusive. Here, we found that RIG-1 undergoes proteasomal degradation after conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5, a family protein of RIG-1 as well as IPS-1, which is also a downstream protein of RIG-1 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.
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