The E3 Ubiquitin Ligase TBK1 Mediates the Degradation of Multiple Picornavirus VP3 Proteins by Phosphorylation and Ubiquitination
| Autor: | Li Dan, Keshan Zhang, Yi Ru, Shaozu Fu, Jingjing Ren, Wenping Yang, Haixue Zheng, Xiangtao Liu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Picornavirus
Viral protein Ubiquitin-Protein Ligases viruses Immunology Picornaviridae Protein Serine-Threonine Kinases medicine.disease_cause Microbiology Gene Knockout Techniques Viral Proteins TANK-binding kinase 1 Ubiquitin Virology medicine Humans Phosphorylation Adaptor Proteins Signal Transducing biology Kinase Lysine Ubiquitination Signal transducing adaptor protein biochemical phenomena metabolism and nutrition biology.organism_classification Immunity Innate Virus-Cell Interactions Ubiquitin ligase Cell biology HEK293 Cells Insect Science Mutation Proteolysis biology.protein Capsid Proteins Sequence Alignment |
| Zdroj: | J Virol |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01438-19 |
| Popis: | TANK-binding kinase 1 (TBK1) is essential for interferon beta (IFN-β) production and innate antiviral immunity. However, other, additional functions of TBK1 have remained elusive. Here, we showed that TBK1 is an E3 ubiquitin ligase that undergoes self-ubiquitylation in vitro in the presence of the E2 enzyme UbcH5c. Further evidence showed that TBK1 could also be self-ubiquitylated in vivo. Importantly, multiple picornavirus VP3 proteins were degraded by TBK1 through its kinase and E3 ubiquitin ligase activity. Mechanistically, TBK1 phosphorylated multiple picornavirus VP3 proteins at serine residues and ubiquitinated them via K63-linked ubiquitination at lysine residues. In addition, the C426 and C605 residues of TBK1 were not essential for TBK1 innate immunity activity; however, these residues were required for degradation of multiple picornavirus VP3 proteins and for its E3 ubiquitin ligase activity. Hence, our findings identified a novel role of TBK1 in regulating the virus life cycle and provided new insights into the molecular mechanisms of TBK1-mediated antiviral response. IMPORTANCE TBK1 is an important adaptor protein required for innate immune response to viruses, but its other functions were unknown. In this study, we found that TBK1 is an E3 ubiquitin ligase that undergoes self-ubiquitylation in vitro in the presence of the E2 enzyme UbcH5c. In addition, multiple picornavirus VP3 proteins were degraded by TBK1 through its kinase and E3 ubiquitin ligase activity. Our report provides evidence that TBK1 plays a role in viral protein degradation. |
| Databáze: | OpenAIRE |
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