Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Artículo científico |
| Language: | en |
| Published: |
Fish & shellfish immunology
2025
|
| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40701449/ |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1868266174415896576 |
|---|---|
| author | Dong, Wenjing Xie, Meina Li, Wenxin Xu, Tianjun Sun, Yuena |
| author_facet | Dong, Wenjing Xie, Meina Li, Wenxin Xu, Tianjun Sun, Yuena Dong, Wenjing Xie, Meina Li, Wenxin Xu, Tianjun Sun, Yuena |
| collection | PubMed - marine biology |
| contents | RNF34 negatively regulates innate immunity via ubiquitin-mediated TAK1 degradation in miiuy croaker (Miichthysmiiuy). Dong, Wenjing Xie, Meina Li, Wenxin Xu, Tianjun Sun, Yuena Animals Immunity, Innate Perciformes Fish Proteins Fish Diseases Ubiquitin-Protein Ligases MAP Kinase Kinase Kinases Rhabdoviridae Infections Rhabdoviridae Gene Expression Regulation Ubiquitin MAP Kinase Kinase Kinase 7 Ubiquitination, an essential post-translational regulatory mechanism, is primarily controlled by E3 ubiquitin ligases that dictate substrate specificity. Following microbial invasion, the innate immune defense mechanism is rapidly activated, wherein transforming growth factor-β-activated kinase 1 (MAP3K7/TAK1), a pivotal node in innate immune signaling, is tightly regulated by E3 ubiquitin ligases that dictate its stability and activity. Among these, Ring Finger Protein 34 (RNF34), a member of the E3 ligase family, has a role in regulating innate immunity in teleost fish that remains uncharacterized. In this study, we systematically investigate how RNF34 modulates this process using miiuy croaker (Miichthys miiuy). Siniperca chuatsi rhabdovirus (SCRV) infection significantly upregulates RNF34 expression, thereby promoting viral replication and suppressing transcription of key antiviral genes, including pro-inflammatory cytokines (IL-8, IL-1β) and interferon-stimulated genes (ISG15, MX1, Viperin). In luciferase reporter assays, this inhibitory effect was associated with RNF34-mediated suppression of the NF-κB/IRF3 signaling pathway. Western blot analysis revealed that RNF34 reduced TAK1 expression in a dose- and time-dependent manner. Ubiquitination assays confirmed that RNF34 can promote the ubiquitination of TAK1, and further experiments revealed that the proteasome inhibitor MG132 can block the degradation of TAK1. These findings indicate that RNF34 mediates the degradation of TAK1 through the ubiquitin-proteasome pathway, thereby acting as a negative regulator of innate immunity and inhibiting the NF-κB and IRF3 signaling pathways in miiuy croaker. This study identifies a crucial negative regulatory molecule in teleost fish. |
| format | Artículo científico |
| id | pubmed_40701449 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Fish & shellfish immunology |
| record_format | pubmed |
| spellingShingle | RNF34 negatively regulates innate immunity via ubiquitin-mediated TAK1 degradation in miiuy croaker (Miichthysmiiuy). Dong, Wenjing Xie, Meina Li, Wenxin Xu, Tianjun Sun, Yuena Animals Immunity, Innate Perciformes Fish Proteins Fish Diseases Ubiquitin-Protein Ligases MAP Kinase Kinase Kinases Rhabdoviridae Infections Rhabdoviridae Gene Expression Regulation Ubiquitin MAP Kinase Kinase Kinase 7 RNF34 negatively regulates innate immunity via ubiquitin-mediated TAK1 degradation in miiuy croaker (Miichthysmiiuy). Dong, Wenjing Xie, Meina Li, Wenxin Xu, Tianjun Sun, Yuena Animals Immunity, Innate Perciformes Fish Proteins Fish Diseases Ubiquitin-Protein Ligases MAP Kinase Kinase Kinases Rhabdoviridae Infections Rhabdoviridae Gene Expression Regulation Ubiquitin MAP Kinase Kinase Kinase 7 Ubiquitination, an essential post-translational regulatory mechanism, is primarily controlled by E3 ubiquitin ligases that dictate substrate specificity. Following microbial invasion, the innate immune defense mechanism is rapidly activated, wherein transforming growth factor-β-activated kinase 1 (MAP3K7/TAK1), a pivotal node in innate immune signaling, is tightly regulated by E3 ubiquitin ligases that dictate its stability and activity. Among these, Ring Finger Protein 34 (RNF34), a member of the E3 ligase family, has a role in regulating innate immunity in teleost fish that remains uncharacterized. In this study, we systematically investigate how RNF34 modulates this process using miiuy croaker (Miichthys miiuy). Siniperca chuatsi rhabdovirus (SCRV) infection significantly upregulates RNF34 expression, thereby promoting viral replication and suppressing transcription of key antiviral genes, including pro-inflammatory cytokines (IL-8, IL-1β) and interferon-stimulated genes (ISG15, MX1, Viperin). In luciferase reporter assays, this inhibitory effect was associated with RNF34-mediated suppression of the NF-κB/IRF3 signaling pathway. Western blot analysis revealed that RNF34 reduced TAK1 expression in a dose- and time-dependent manner. Ubiquitination assays confirmed that RNF34 can promote the ubiquitination of TAK1, and further experiments revealed that the proteasome inhibitor MG132 can block the degradation of TAK1. These findings indicate that RNF34 mediates the degradation of TAK1 through the ubiquitin-proteasome pathway, thereby acting as a negative regulator of innate immunity and inhibiting the NF-κB and IRF3 signaling pathways in miiuy croaker. This study identifies a crucial negative regulatory molecule in teleost fish. |
| title | RNF34 negatively regulates innate immunity via ubiquitin-mediated TAK1 degradation in miiuy croaker (Miichthysmiiuy). |
| topic | Animals Immunity, Innate Perciformes Fish Proteins Fish Diseases Ubiquitin-Protein Ligases MAP Kinase Kinase Kinases Rhabdoviridae Infections Rhabdoviridae Gene Expression Regulation Ubiquitin MAP Kinase Kinase Kinase 7 |
| url | https://pubmed.ncbi.nlm.nih.gov/40701449/ |