Spermidine reduces ISGylation and enhances ISG15–USP18 interaction
Abstract The expression of ubiquitin-like molecule interferon-stimulated gene 15 kDa (ISG15) and its post-translational modification (ISGylation) are significantly activated by interferons or pathogen infections, highlighting their roles in innate immune responses. Over 1100 proteins have been ident...
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Nature Portfolio
2025-05-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-01425-0 |
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| author | Haruka Etori Riko Asoshina Takayuki Obita Fumihiko Okumura |
| author_facet | Haruka Etori Riko Asoshina Takayuki Obita Fumihiko Okumura |
| author_sort | Haruka Etori |
| collection | DOAJ |
| description | Abstract The expression of ubiquitin-like molecule interferon-stimulated gene 15 kDa (ISG15) and its post-translational modification (ISGylation) are significantly activated by interferons or pathogen infections, highlighting their roles in innate immune responses. Over 1100 proteins have been identified as ISGylated. ISG15 is removed from substrates by interferon-induced ubiquitin-specific peptidase 18 (USP18) or severe acute respiratory syndrome coronavirus 2-derived papain-like protease. High ISGylation levels may help prevent the spread of coronavirus disease 2019 (COVID-19). Polyamines (spermidine and spermine) exhibit anti-inflammatory, antioxidant, and mitochondrial functions. However, the relationship between nutrients and ISGylation remains unclear. This study assessed the effects of spermine and spermidine on ISGylation. MCF10A and A549 cells were treated with interferon-alpha, spermine, or spermidine, and the expression levels of various proteins and ISGylation were measured. Spermine and spermidine dose-dependently reduced ISGylation. Additionally, spermidine directly interacted with ISG15 and USP18, enhancing their interaction and potentially reducing ISGylation. Therefore, spermidine may prevent ISGylation-related immune responses. |
| format | Article |
| id | doaj-art-64449e19d66846f5a6f1213db97c830c |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-64449e19d66846f5a6f1213db97c830c2025-08-20T03:48:18ZengNature PortfolioScientific Reports2045-23222025-05-0115111810.1038/s41598-025-01425-0Spermidine reduces ISGylation and enhances ISG15–USP18 interactionHaruka Etori0Riko Asoshina1Takayuki Obita2Fumihiko Okumura3Department of Food and Health Sciences, International College of Arts and Sciences, Fukuoka Women’s UniversityDepartment of Food and Health Sciences, International College of Arts and Sciences, Fukuoka Women’s UniversityFaculty of Pharmaceutical Sciences, University of ToyamaDepartment of Food and Health Sciences, International College of Arts and Sciences, Fukuoka Women’s UniversityAbstract The expression of ubiquitin-like molecule interferon-stimulated gene 15 kDa (ISG15) and its post-translational modification (ISGylation) are significantly activated by interferons or pathogen infections, highlighting their roles in innate immune responses. Over 1100 proteins have been identified as ISGylated. ISG15 is removed from substrates by interferon-induced ubiquitin-specific peptidase 18 (USP18) or severe acute respiratory syndrome coronavirus 2-derived papain-like protease. High ISGylation levels may help prevent the spread of coronavirus disease 2019 (COVID-19). Polyamines (spermidine and spermine) exhibit anti-inflammatory, antioxidant, and mitochondrial functions. However, the relationship between nutrients and ISGylation remains unclear. This study assessed the effects of spermine and spermidine on ISGylation. MCF10A and A549 cells were treated with interferon-alpha, spermine, or spermidine, and the expression levels of various proteins and ISGylation were measured. Spermine and spermidine dose-dependently reduced ISGylation. Additionally, spermidine directly interacted with ISG15 and USP18, enhancing their interaction and potentially reducing ISGylation. Therefore, spermidine may prevent ISGylation-related immune responses.https://doi.org/10.1038/s41598-025-01425-0InterferonISGylationInterferon-stimulated gene 15 kDaPolyamineSpermidine |
| spellingShingle | Haruka Etori Riko Asoshina Takayuki Obita Fumihiko Okumura Spermidine reduces ISGylation and enhances ISG15–USP18 interaction Scientific Reports Interferon ISGylation Interferon-stimulated gene 15 kDa Polyamine Spermidine |
| title | Spermidine reduces ISGylation and enhances ISG15–USP18 interaction |
| title_full | Spermidine reduces ISGylation and enhances ISG15–USP18 interaction |
| title_fullStr | Spermidine reduces ISGylation and enhances ISG15–USP18 interaction |
| title_full_unstemmed | Spermidine reduces ISGylation and enhances ISG15–USP18 interaction |
| title_short | Spermidine reduces ISGylation and enhances ISG15–USP18 interaction |
| title_sort | spermidine reduces isgylation and enhances isg15 usp18 interaction |
| topic | Interferon ISGylation Interferon-stimulated gene 15 kDa Polyamine Spermidine |
| url | https://doi.org/10.1038/s41598-025-01425-0 |
| work_keys_str_mv | AT harukaetori spermidinereducesisgylationandenhancesisg15usp18interaction AT rikoasoshina spermidinereducesisgylationandenhancesisg15usp18interaction AT takayukiobita spermidinereducesisgylationandenhancesisg15usp18interaction AT fumihikookumura spermidinereducesisgylationandenhancesisg15usp18interaction |