The ubiquitin ligase Pellino1 targets STAT3 to regulate macrophage-mediated inflammation and tumor development
Abstract Receptor-mediated signaling could be modulated by ubiquitination of pathway intermediates, but the role of such modification in the pathogenesis of inflammation and inflammation-related cancer is lesser known. The ubiquitin ligase Pellino1 has been shown to modulate immune signals by enabli...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56440-6 |
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| author | Soeun Hwang Junhee Park Seo-Young Koo Si-Yeon Lee Yunju Jo Dongryeol Ryu Heounjeong Go Chang-Woo Lee |
| author_facet | Soeun Hwang Junhee Park Seo-Young Koo Si-Yeon Lee Yunju Jo Dongryeol Ryu Heounjeong Go Chang-Woo Lee |
| author_sort | Soeun Hwang |
| collection | DOAJ |
| description | Abstract Receptor-mediated signaling could be modulated by ubiquitination of pathway intermediates, but the role of such modification in the pathogenesis of inflammation and inflammation-related cancer is lesser known. The ubiquitin ligase Pellino1 has been shown to modulate immune signals by enabling various immune cells to respond to their receptor signals effectively. Here, we show that Pellino1 levels are elevated in patients with colitis, patients with colitis-associated colon cancer (CAC), and murine models of these conditions. In a monocyte-specific Pellino1 knock-out mouse model, we find reduced macrophage migration and activation, leading to attenuated development of colitis and CAC in male mice. Mechanistically, Pellino1 targets STAT3 for lysine 63-mediated ubiquitination, resulting in pathogenic activation of STAT3 signaling. Taken together, our findings reveal a macrophage-specific ubiquitination signaling axis in colitis and CAC development and suggest that Pellino1 is a potential candidate for treating chronic inflammation and inflammation-related cancer. |
| format | Article |
| id | doaj-art-9025912a4ea44d789af2a23760061fdc |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9025912a4ea44d789af2a23760061fdc2025-02-02T12:32:34ZengNature PortfolioNature Communications2041-17232025-02-0116112010.1038/s41467-025-56440-6The ubiquitin ligase Pellino1 targets STAT3 to regulate macrophage-mediated inflammation and tumor developmentSoeun Hwang0Junhee Park1Seo-Young Koo2Si-Yeon Lee3Yunju Jo4Dongryeol Ryu5Heounjeong Go6Chang-Woo Lee7Department of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST)Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST)Department of Pathology, University of Ulsan College of Medicine, Asan Medical CenterDepartment of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of MedicineAbstract Receptor-mediated signaling could be modulated by ubiquitination of pathway intermediates, but the role of such modification in the pathogenesis of inflammation and inflammation-related cancer is lesser known. The ubiquitin ligase Pellino1 has been shown to modulate immune signals by enabling various immune cells to respond to their receptor signals effectively. Here, we show that Pellino1 levels are elevated in patients with colitis, patients with colitis-associated colon cancer (CAC), and murine models of these conditions. In a monocyte-specific Pellino1 knock-out mouse model, we find reduced macrophage migration and activation, leading to attenuated development of colitis and CAC in male mice. Mechanistically, Pellino1 targets STAT3 for lysine 63-mediated ubiquitination, resulting in pathogenic activation of STAT3 signaling. Taken together, our findings reveal a macrophage-specific ubiquitination signaling axis in colitis and CAC development and suggest that Pellino1 is a potential candidate for treating chronic inflammation and inflammation-related cancer.https://doi.org/10.1038/s41467-025-56440-6 |
| spellingShingle | Soeun Hwang Junhee Park Seo-Young Koo Si-Yeon Lee Yunju Jo Dongryeol Ryu Heounjeong Go Chang-Woo Lee The ubiquitin ligase Pellino1 targets STAT3 to regulate macrophage-mediated inflammation and tumor development Nature Communications |
| title | The ubiquitin ligase Pellino1 targets STAT3 to regulate macrophage-mediated inflammation and tumor development |
| title_full | The ubiquitin ligase Pellino1 targets STAT3 to regulate macrophage-mediated inflammation and tumor development |
| title_fullStr | The ubiquitin ligase Pellino1 targets STAT3 to regulate macrophage-mediated inflammation and tumor development |
| title_full_unstemmed | The ubiquitin ligase Pellino1 targets STAT3 to regulate macrophage-mediated inflammation and tumor development |
| title_short | The ubiquitin ligase Pellino1 targets STAT3 to regulate macrophage-mediated inflammation and tumor development |
| title_sort | ubiquitin ligase pellino1 targets stat3 to regulate macrophage mediated inflammation and tumor development |
| url | https://doi.org/10.1038/s41467-025-56440-6 |
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