| Tartalom: |
http://dx.doi.org/10.1073/pnas.1505690112 |
| Archívum: |
MTA Könyvtár |
| Gyűjtemény: |
Status = Published
Type = Article
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| Cím: |
Type I IFN induces protein ISGylation to enhance cytokine expression and augments colonic inflammation
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| Létrehozó: |
Fan, J-B.
Miyauchi-Ishida, S.
Arimoto, K-I.
Liu, D.
Yan, M.
Györffy, Balázs
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| Dátum: |
2015
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| Téma: |
RB Pathology / patológia, kórtan
RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkológia
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| Tartalmi leírás: |
Type I IFNs have broad activity in tissue inflammation and malignant progression that depends on the expression of IFN-stimulated genes (ISGs). ISG15, one such ISG, can form covalent conjugates to many cellular proteins, a process termed "protein ISGylation." Although type I IFNs are involved in multiple inflammatory disorders, the role of protein ISGylation during inflammation has not been evaluated. Here we report that protein ISGylation exacerbates intestinal inflammation and colitis-associated colon cancer in mice. Mechanistically, we demonstrate that protein ISGylation negatively regulates the ubiquitin-proteasome system, leading to increased production of IFN-induced reactive oxygen species (ROS). The increased cellular ROS then enhances LPS-induced activation of p38 MAP kinase and the expression of inflammation-related cytokines in macrophages. Thus our studies reveal a regulatory role for protein ISGylation in colonic inflammation and its related malignant progression, indicating that targeting ubiquitin-activating enzyme E1 homolog has therapeutic potential in treating inflammatory diseases.
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| Típus: |
Article
PeerReviewed
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| Formátum: |
text
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| Azonosító: |
Fan, J-B. and Miyauchi-Ishida, S. and Arimoto, K-I. and Liu, D. and Yan, M. and Györffy, Balázs (2015) Type I IFN induces protein ISGylation to enhance cytokine expression and augments colonic inflammation. Proceedings of the National Academy of Sciences, 112 (46). pp. 14313-14318. ISSN 0027-8424
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