ArticleCell death & disease2025
Deubiquitination enzyme USP35 negatively regulates MAVS signaling to inhibit anti-tumor immunity.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- ATG13 promotes K63-linked polyubiquitination of MAVS via ASB1 to restrict influenza A virus replication.Emerging microbes & infections · 2026Article
- Deubiquitinase USP35 regulates MDM4 degradation to promote endothelial ferroptosis and renal injury progression.Cell death discovery · 2026Article
- The deubiquitinase USP35: from an oncogenic hub to a therapeutic target in human cancers.Frontiers in oncology · 2026Review
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- Comprehensive pan-cancer analysis of USP35 and validation of its role in gastric cancer.Human genomics · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
The RIG-I/MAVS signaling stimulates anti-tumor immunity by triggering the production of inflammatory cytokines. Activation of MAVS induced by viral RNA and RIG-I binding is critical in this pathway. However, the molecular mechanism underlying the regulation of MAVS activity and its function in anti-tumor immunity is not fully understood. Here, we report that the ubiquitin-specific protease 35 (USP35) negatively regulates the MAVS signaling. Mechanistically, USP35 interacts with MAVS and removes its K63-linked polyubiquitin chains, thereby inhibiting viral-induced MAVS-TBK1-IRF3 activation and downstream inflammatory gene expression. Importantly, depletion of USP35 significantly enhances the anti-tumor immunity and synergizes with oncolytic virotherapy to suppress xenograft tumor growth of melanoma cells. Thus, our study identifies USP35 as a negative regulator of MAVS signaling, representing a potential immunosuppressive factor in cutaneous melanoma.
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Registered trials
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