Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation
| العنوان: | Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation |
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| المؤلفون: | Benjamin J. Swanson, John M. Asara, Audrey J. Lazenby, Jeffrey D. Singer, Wei Gong, Haitao Wen, Laura E. Herring, Lupeng Li, Zhibin Zhang, Xinghui Li |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | The Rockefeller University Press, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, STAT3 Transcription Factor, Immunology, N-Acetylglucosaminyltransferases, environment and public health, Article, 03 medical and health sciences, Mice, Gene expression, Immunology and Allergy, Animals, Phosphorylation, STAT3, Research Articles, biology, Chemistry, Cullin Proteins, Enteritis, Ubiquitin ligase, Mice, Inbred C57BL, 030104 developmental biology, biology.protein, Cancer research, STAT protein, Protein Processing, Post-Translational, Cullin |
| الوصف: | Li et al. show that OGT-mediated STAT3 O-GlcNAcylation, which is modulated by CUL3-Nrf2 signaling, negatively regulates STAT3 phosphorylation and IL-10 production in macrophages and exacerbates experimental colitis and colitis-associated cancer. Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. However, the molecular mechanism that modulates STAT3 phosphorylation and activation is not fully understood. Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2–related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. Thus, this study identifies a new form of posttranslational modification of STAT3, modulating its phosphorylation, and suggests the importance of immunometabolism on colonic inflammation and tumorigenesis. |
| اللغة: | English |
| تدمد: | 1540-9538 0022-1007 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::769d89cd3c0890b953f2b224ae4b6135Test http://europepmc.org/articles/PMC5379975Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....769d89cd3c0890b953f2b224ae4b6135 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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