期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 15, 页码 5646-5651出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1401674111
关键词
signal transduction; cytoplasmic puncta
资金
- Japanese Ministry of Education, Culture, Sports, Science and Technology
- Cabinet Office, Government of Japan
- Japan Society for the Promotion of Science Funding Program for World-Leading Innovative Research and Development on Science and Technology FIRST Program
- National Institutes of Health [P01-AI070167]
- STFC [ST/J001511/1] Funding Source: UKRI
The RIG-I-like receptors, retinoic acid inducible gene-1 (RIG-I), melanoma differentiation-associated protein 5, and laboratory of genetics and physiology-2, are cytoplasmic sensors for RNA viruses that mediate the antiviral innate immune responses. We demonstrate that really interesting new gene-finger domain-and K homology domain-containing MEX3C regulates RIG-I function. MEX3C colocalizes with RIG-I in the stress granules of virally infected cells, and its overexpression causes the lysine-63-linked ubiquitination of RIG-I and activates IFN-beta promoter. Embryonic fibroblast cells, macrophages, and conventional dendritic cells derived from Mex3c-deficient mice showed defective production of type I IFN after infection with RNA viruses that are recognized by RIG-I. These results demonstrate that MEX3C is an E3 ubiquitin ligase that modifies RIG-I in stress granules and plays a critical role in eliciting antiviral immune responses.
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