PARP7 inhibition stabilizes STAT1/STAT2 and relieves experimental autoimmune encephalomyelitis in mice
Summary: The regulation of type I interferon signaling is crucial for precisely tuning the innate immune response to combat pathogen invasions, fight cancer, and prevent autoimmune diseases. PARP7, a mono-ADP-ribosyltransferase also called TiPARP (tetrachlorodibenzo-p-dioxin [TCDD]-inducible PARP),...
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| Language: | English |
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Elsevier
2025-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725009015 |
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| author | Jiashu Xu Tao Yu Zongwei Yue Xuan Lu Yandong Zhang Lei Wang Samaneh Shabani Åhrling Michael R. Smith Yan Chun Li Jason Matthews Hening Lin |
| author_facet | Jiashu Xu Tao Yu Zongwei Yue Xuan Lu Yandong Zhang Lei Wang Samaneh Shabani Åhrling Michael R. Smith Yan Chun Li Jason Matthews Hening Lin |
| author_sort | Jiashu Xu |
| collection | DOAJ |
| description | Summary: The regulation of type I interferon signaling is crucial for precisely tuning the innate immune response to combat pathogen invasions, fight cancer, and prevent autoimmune diseases. PARP7, a mono-ADP-ribosyltransferase also called TiPARP (tetrachlorodibenzo-p-dioxin [TCDD]-inducible PARP), is reported to inhibit the production of type I interferons. Here, we find that PARP7 suppresses type I interferon signaling instead of interferon production. PARP7 ADP-ribosylates and promotes the ubiquitination of signal transducer and activator of transcription 1 (STAT1) and STAT2, which recruits p62 to promote the degradation of STAT1 and STAT2 through autophagy. By reducing STAT1 and STAT2 levels, PARP7 decreases type I interferon signaling. We further show that the inhibition of PARP7 promotes type I interferon signaling and relieves experimental autoimmune encephalomyelitis (EAE) symptoms in mice. Our findings revealed a molecular mechanism via which PARP7 suppresses type I interferon signaling, offering insights into the immune-modulatory function of PARP7 and suggesting PARP7 inhibition as a potential treatment strategy for multiple sclerosis. |
| format | Article |
| id | doaj-art-fc03c23e7ed14aa9b9392c73e8b50b0f |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-fc03c23e7ed14aa9b9392c73e8b50b0f2025-08-20T03:36:35ZengElsevierCell Reports2211-12472025-08-0144811613010.1016/j.celrep.2025.116130PARP7 inhibition stabilizes STAT1/STAT2 and relieves experimental autoimmune encephalomyelitis in miceJiashu Xu0Tao Yu1Zongwei Yue2Xuan Lu3Yandong Zhang4Lei Wang5Samaneh Shabani Åhrling6Michael R. Smith7Yan Chun Li8Jason Matthews9Hening Lin10Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA; Department of Medicine and Department of Chemistry, The University of Chicago, Chicago, IL 60637, USADepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USADepartment of Medicine and Department of Chemistry, The University of Chicago, Chicago, IL 60637, USADepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA; Department of Medicine and Department of Chemistry, The University of Chicago, Chicago, IL 60637, USADepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA; Department of Medicine and Department of Chemistry, The University of Chicago, Chicago, IL 60637, USADepartment of Medicine, The University of Chicago, Chicago, IL 60637, USADepartment of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Sognsvannsveien 9, 0372 Oslo, Norway; Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, CanadaDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USADepartment of Medicine, The University of Chicago, Chicago, IL 60637, USADepartment of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Sognsvannsveien 9, 0372 Oslo, Norway; Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, CanadaDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA; Department of Medicine and Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, Department of Medicine and Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA; Corresponding authorSummary: The regulation of type I interferon signaling is crucial for precisely tuning the innate immune response to combat pathogen invasions, fight cancer, and prevent autoimmune diseases. PARP7, a mono-ADP-ribosyltransferase also called TiPARP (tetrachlorodibenzo-p-dioxin [TCDD]-inducible PARP), is reported to inhibit the production of type I interferons. Here, we find that PARP7 suppresses type I interferon signaling instead of interferon production. PARP7 ADP-ribosylates and promotes the ubiquitination of signal transducer and activator of transcription 1 (STAT1) and STAT2, which recruits p62 to promote the degradation of STAT1 and STAT2 through autophagy. By reducing STAT1 and STAT2 levels, PARP7 decreases type I interferon signaling. We further show that the inhibition of PARP7 promotes type I interferon signaling and relieves experimental autoimmune encephalomyelitis (EAE) symptoms in mice. Our findings revealed a molecular mechanism via which PARP7 suppresses type I interferon signaling, offering insights into the immune-modulatory function of PARP7 and suggesting PARP7 inhibition as a potential treatment strategy for multiple sclerosis.http://www.sciencedirect.com/science/article/pii/S2211124725009015CP: Molecular biologyCP: Neuroscience |
| spellingShingle | Jiashu Xu Tao Yu Zongwei Yue Xuan Lu Yandong Zhang Lei Wang Samaneh Shabani Åhrling Michael R. Smith Yan Chun Li Jason Matthews Hening Lin PARP7 inhibition stabilizes STAT1/STAT2 and relieves experimental autoimmune encephalomyelitis in mice Cell Reports CP: Molecular biology CP: Neuroscience |
| title | PARP7 inhibition stabilizes STAT1/STAT2 and relieves experimental autoimmune encephalomyelitis in mice |
| title_full | PARP7 inhibition stabilizes STAT1/STAT2 and relieves experimental autoimmune encephalomyelitis in mice |
| title_fullStr | PARP7 inhibition stabilizes STAT1/STAT2 and relieves experimental autoimmune encephalomyelitis in mice |
| title_full_unstemmed | PARP7 inhibition stabilizes STAT1/STAT2 and relieves experimental autoimmune encephalomyelitis in mice |
| title_short | PARP7 inhibition stabilizes STAT1/STAT2 and relieves experimental autoimmune encephalomyelitis in mice |
| title_sort | parp7 inhibition stabilizes stat1 stat2 and relieves experimental autoimmune encephalomyelitis in mice |
| topic | CP: Molecular biology CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725009015 |
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