c-Ski is a novel repressor of NF-κB through interaction with p65 and HDAC1 in U937 cells
Abstract The nuclear factor kappa B (NF-κB) signalling pathway plays a crucial role in the regulation of inflammation, and previous research from our lab and others suggests that c-Ski has potential anti-inflammatory effects. However, the role and mechanism of c-Ski, which are related to the regulat...
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| Format: | Article |
| Language: | English |
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BMC
2025-04-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02178-z |
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| author | Yan Peng Ren-Ping Xiong Bo Wang Xing Chen Ya-Lie Ning Yan Zhao Nan Yang Jing Zhang Chang-Hong Li Yuan-Guo Zhou Ping Li |
| author_facet | Yan Peng Ren-Ping Xiong Bo Wang Xing Chen Ya-Lie Ning Yan Zhao Nan Yang Jing Zhang Chang-Hong Li Yuan-Guo Zhou Ping Li |
| author_sort | Yan Peng |
| collection | DOAJ |
| description | Abstract The nuclear factor kappa B (NF-κB) signalling pathway plays a crucial role in the regulation of inflammation, and previous research from our lab and others suggests that c-Ski has potential anti-inflammatory effects. However, the role and mechanism of c-Ski, which are related to the regulation of the NF-κB pathway, are still unclear. Here, U937 cells were used, and increasing c-Ski protein levels inhibited inflammatory factor production, invasion, and phagocytosis. The anti-inflammatory effect of c-Ski was similar to that of hormones. Subsequently, immunoprecipitation (IP), Western blot (WB), electrophoretic mobility shift assays (EMSAs), and dual-luciferase reporter assays were used to determine whether increasing c-Ski protein levels could increase c-Ski binding to NF-κB p65 (p65), leading to a decrease in the acetylation level and transcriptional activity of p65. Conversely, decreased p65 expression through targeted small interfering RNA (siRNA) caused the loss of the anti-inflammatory effects of c-Ski. Furthermore, immunoprecipitation confirmed the mutual interaction of c-Ski with HDAC1 and p65, and WB revealed that the anti-inflammatory effect of c-Ski was achieved through the deacetylation of p65 by HDAC1 combined with HDAC1 siRNA and inhibitors. Additionally, through quantitative proteomic analysis, we determined that increasing c-Ski levels had inhibitory effects on the NF-κB pathway. Finally, similar results were also obtained using primary bone marrow-derived macrophages (BMDMs). These findings not only confirm the anti-inflammatory effect of c-Ski but also reveal novel molecular pathways and regulatory molecules of c-Ski, which may be promising targets for direct intervention in the inflammatory response through regulation of c-Ski. |
| format | Article |
| id | doaj-art-73d4159a650041638150d63ce6f12713 |
| institution | OA Journals |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-73d4159a650041638150d63ce6f127132025-08-20T02:25:41ZengBMCCell Communication and Signaling1478-811X2025-04-0123111710.1186/s12964-025-02178-zc-Ski is a novel repressor of NF-κB through interaction with p65 and HDAC1 in U937 cellsYan Peng0Ren-Ping Xiong1Bo Wang2Xing Chen3Ya-Lie Ning4Yan Zhao5Nan Yang6Jing Zhang7Chang-Hong Li8Yuan-Guo Zhou9Ping Li10State Key Laboratory of Trauma, Burn and Combined Injury, Department of Army Occupational Disease, Daping Hospital, Army Medical University (Third Military Medical University)State Key Laboratory of Trauma, Burn and Combined Injury, Department of Army Occupational Disease, Daping Hospital, Army Medical University (Third Military Medical University)State Key Laboratory of Trauma, Burn and Combined Injury, Department of Army Occupational Disease, Daping Hospital, Army Medical University (Third Military Medical University)State Key Laboratory of Trauma, Burn and Combined Injury, Department of Army Occupational Disease, Daping Hospital, Army Medical University (Third Military Medical University)State Key Laboratory of Trauma, Burn and Combined Injury, Department of Army Occupational Disease, Daping Hospital, Army Medical University (Third Military Medical University)State Key Laboratory of Trauma, Burn and Combined Injury, Department of Army Occupational Disease, Daping Hospital, Army Medical University (Third Military Medical University)State Key Laboratory of Trauma, Burn and Combined Injury, Department of Army Occupational Disease, Daping Hospital, Army Medical University (Third Military Medical University)State Key Laboratory of Trauma, Burn and Combined Injury, Department of Army Occupational Disease, Daping Hospital, Army Medical University (Third Military Medical University)State Key Laboratory of Trauma, Burn and Combined Injury, Department of Army Occupational Disease, Daping Hospital, Army Medical University (Third Military Medical University)State Key Laboratory of Trauma, Burn and Combined Injury, Department of Army Occupational Disease, Daping Hospital, Army Medical University (Third Military Medical University)State Key Laboratory of Trauma, Burn and Combined Injury, Department of Army Occupational Disease, Daping Hospital, Army Medical University (Third Military Medical University)Abstract The nuclear factor kappa B (NF-κB) signalling pathway plays a crucial role in the regulation of inflammation, and previous research from our lab and others suggests that c-Ski has potential anti-inflammatory effects. However, the role and mechanism of c-Ski, which are related to the regulation of the NF-κB pathway, are still unclear. Here, U937 cells were used, and increasing c-Ski protein levels inhibited inflammatory factor production, invasion, and phagocytosis. The anti-inflammatory effect of c-Ski was similar to that of hormones. Subsequently, immunoprecipitation (IP), Western blot (WB), electrophoretic mobility shift assays (EMSAs), and dual-luciferase reporter assays were used to determine whether increasing c-Ski protein levels could increase c-Ski binding to NF-κB p65 (p65), leading to a decrease in the acetylation level and transcriptional activity of p65. Conversely, decreased p65 expression through targeted small interfering RNA (siRNA) caused the loss of the anti-inflammatory effects of c-Ski. Furthermore, immunoprecipitation confirmed the mutual interaction of c-Ski with HDAC1 and p65, and WB revealed that the anti-inflammatory effect of c-Ski was achieved through the deacetylation of p65 by HDAC1 combined with HDAC1 siRNA and inhibitors. Additionally, through quantitative proteomic analysis, we determined that increasing c-Ski levels had inhibitory effects on the NF-κB pathway. Finally, similar results were also obtained using primary bone marrow-derived macrophages (BMDMs). These findings not only confirm the anti-inflammatory effect of c-Ski but also reveal novel molecular pathways and regulatory molecules of c-Ski, which may be promising targets for direct intervention in the inflammatory response through regulation of c-Ski.https://doi.org/10.1186/s12964-025-02178-zc-SkiNF-κBInflammationp65HDAC1 |
| spellingShingle | Yan Peng Ren-Ping Xiong Bo Wang Xing Chen Ya-Lie Ning Yan Zhao Nan Yang Jing Zhang Chang-Hong Li Yuan-Guo Zhou Ping Li c-Ski is a novel repressor of NF-κB through interaction with p65 and HDAC1 in U937 cells Cell Communication and Signaling c-Ski NF-κB Inflammation p65 HDAC1 |
| title | c-Ski is a novel repressor of NF-κB through interaction with p65 and HDAC1 in U937 cells |
| title_full | c-Ski is a novel repressor of NF-κB through interaction with p65 and HDAC1 in U937 cells |
| title_fullStr | c-Ski is a novel repressor of NF-κB through interaction with p65 and HDAC1 in U937 cells |
| title_full_unstemmed | c-Ski is a novel repressor of NF-κB through interaction with p65 and HDAC1 in U937 cells |
| title_short | c-Ski is a novel repressor of NF-κB through interaction with p65 and HDAC1 in U937 cells |
| title_sort | c ski is a novel repressor of nf κb through interaction with p65 and hdac1 in u937 cells |
| topic | c-Ski NF-κB Inflammation p65 HDAC1 |
| url | https://doi.org/10.1186/s12964-025-02178-z |
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