MLL5 suppresses antiviral innate immune response by facilitating STUB1-mediated RIG-I degradation
Autor: | Lih-Wen Deng, Peipei Zhou, Lulu Liu, Xiaodan Ding, Guangxun Meng, Xinhui Hui, Bin Li, Fajian Hou, Xiujie Yuan, Jin Zhong, Hui Xiao, Xiaoling Wan, Wei Zhang, Yan Zhang |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Cytoplasm Proteasome Endopeptidase Complex Ubiquitin-Protein Ligases viruses Science General Physics and Astronomy chemical and pharmacologic phenomena Biology Virus Replication Antiviral Agents General Biochemistry Genetics and Molecular Biology Vesicular stomatitis Indiana virus Article 03 medical and health sciences Mice Immune system RNA interference Immunity Rhabdoviridae Infections Animals Humans STUB1 Multidisciplinary Innate immune system RIG-I Ubiquitination General Chemistry Histone-Lysine N-Methyltransferase biochemical phenomena metabolism and nutrition biology.organism_classification Immunity Innate Ubiquitin ligase Cell biology DNA-Binding Proteins Mice Inbred C57BL 030104 developmental biology HEK293 Cells Vesicular stomatitis virus biology.protein DEAD Box Protein 58 Female RNA Interference CRISPR-Cas Systems DNA Damage Signal Transduction |
Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) Nature Communications |
ISSN: | 2041-1723 |
Popis: | Trithorax group protein MLL5 is an important epigenetic modifier that controls cell cycle progression, chromatin architecture maintenance, and hematopoiesis. However, whether MLL5 has a role in innate antiviral immunity is largely unknown. Here we show that MLL5 suppresses the RIG-I-mediated anti-viral immune response. Mll5-deficient mice infected with vesicular stomatitis virus show enhanced anti-viral innate immunity, reduced morbidity, and viral load. Mechanistically, a fraction of MLL5 located in the cytoplasm interacts with both RIG-I and its E3 ubiquitin ligase STUB1, which promotes K48-linked polyubiquitination and proteasomal degradation of RIG-I. MLL5 deficiency attenuates the RIG-I and STUB1 association, reducing K48-linked polyubiquitination and accumulation of RIG-I protein in cells. Upon virus infection, nuclear MLL5 protein translocates from the nucleus to the cytoplasm inducing STUB1-mediated degradation of RIG-I. Our study uncovers a previously unrecognized role for MLL5 in antiviral innate immune responses and suggests a new target for controlling viral infection. MLL5 is an essential epigenetic modifier involved in cell cycle progression, chromatin architecture and hematopoiesis. Here the authors establish that MLL5 suppresses the innate immune response in a murine model of virus infection by targeting and promoting degradation of RIG-I. |
Databáze: | OpenAIRE |
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