Academic Journal
PBLD enhances antiviral innate immunity by promoting the p53-USP4-MAVS signaling axis.
| العنوان: | PBLD enhances antiviral innate immunity by promoting the p53-USP4-MAVS signaling axis. |
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| المؤلفون: | Chu, Fengyun, Hou, Peili, Zhu, Hongchao, Gao, Yan, Wang, Xiaomeng, He, Wenqi, Ren, Juan, Li, Min, Liu, Yu, Chang He, Daniel, Wang, Hongmei, Gao, Yuwei, He, Hongbin |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America, 121(49) |
| بيانات النشر: | Proceedings of the National Academy of Sciences |
| سنة النشر: | 2024 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | K48-linked ubiquitin chains, macrophages, promote viral replication, response to virus infection, IFN-I response, RNA virus infection, research, phenazine biosynthesis-like domain-containing protein, ubiquitin chains, target, domain-containing proteins, findings, upregulation, molecules, ubiquitin-specific protease 4, RNA, pathway, activity, RLR, susceptible to RNA virus infection, transcription, primary macrophages, MAV, upregulation of p53, protein, study, treat RNA virus infections, viral replication, innate immune response, p53 |
| الوصف: | Phenazine biosynthesis-like domain-containing protein (PBLD) has been reported to be involved in the development of many cancers. However, whether PBLD regulates innate immune responses and viral replication is unclear. In this study, although it was found that the activity of PBLD extends to other PRRs, we focused on the RLR pathway activated via the p53-USP4-MAVS axis in response to virus infections. We found that PBLD deubiquitinates and stabilizes MAVS through ubiquitin-specific protease 4 (USP4) to promote antiviral innate immunity. Mechanistically, PBLD activates the transcription of USP4 via the upregulation of p53. USP4, which is a MAVS-interacting protein, substantially stabilizes the MAVS protein by deconjugating K48-linked ubiquitination chains from the MAVS protein at Lys461 during RNA virus infection. Most intriguingly, RNA virus-infected primary macrophages (peritoneal macrophages, PMs, and bone marrow-derived macrophages, BMDMs) and internal organ cells (lung and liver) from PBLD-deficient mice suppress the IFN-I response and promote viral replication. Notably, PBLD-deficient mice are more susceptible to RNA virus infection than their wild-type littermates. Our findings highlight a unique function of PBLD in antiviral innate immunity through the p53-USP4-MAVS signaling, providing a preliminary basis for research on PBLD as a target molecule for treating RNA virus infection. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://cdr.lib.unc.edu/downloads/fq978821k?file=thumbnail; https://cdr.lib.unc.edu/downloads/fq978821k |
| DOI: | 10.17615/66nm-5h08 |
| الاتاحة: | https://doi.org/10.17615/66nm-5h08 https://cdr.lib.unc.edu/downloads/fq978821k?file=thumbnail https://cdr.lib.unc.edu/downloads/fq978821k |
| Rights: | http://rightsstatements.org/vocab/InC/1.0/ ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| رقم الانضمام: | edsbas.58946D35 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/66nm-5h08 |
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