رسالة جامعية
The role of linear ubiquitination in toll-like receptor 3 signalling
| العنوان: | The role of linear ubiquitination in toll-like receptor 3 signalling |
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| المؤلفون: | Zinngrebe, Julia |
| المساهمون: | Debatin, Klaus-Michael, Gierschik, Peter |
| بيانات النشر: | Universität Ulm |
| سنة النشر: | 2017 |
| المجموعة: | OPARU (OPen Access Repository of Ulm University) |
| مصطلحات موضوعية: | Ubiquitination, LUBAC, SHARPIN, HOIL-1, HOIP, cpdm, TLR3, Innate immunity, DDC 610 / Medicine & health, Ubiquitin-protein ligase complexes, Immunity, innate, Mice, Toll-like receptor 3, Ubiquitinierung, Toll-like-Rezeptoren, Angeborene Immunität |
| الوصف: | Recently, linear ubiquitination mediated by the linear ubiquitin chain assembly complex (LUBAC), comprising SHANK-associated RBCK1 homology-domain-interacting protein (SHARPIN), Heme-oxidised IRP2 ubiquitin ligase-1 (HOIL-1) and HOIL-1-interacting protein (HOIP), was identified as critical regulator of inflammation. Toll-like receptor (TLR) 3 is activated by double-stranded RNA (dsRNA) and plays a crucial role in the detection of both, viral infection and tissue damage. This thesis establishes linear ubiquitination mediated by LUBAC as crucial regulator of TLR3 signalling. LUBAC enables TLR3-mediated gene activation and controls TLR3-induced cell death. In addition, all three LUBAC components were identified as new components of the TLR3-signalling complex (TLR3-SC). Moreover, LUBAC also formed part of the previously unrecognised TLR3-induced death-inducing signalling complex (DISC) which is devoid of TLR3 but whose formation is induced by TLR3 stimulation. Mice with perturbed linear ubiquitination due to absence of the LUBAC component SHARPIN suffer from severe chronic skin inflammation. Co-ablation of Tlr3 ameliorated dermatitis caused by SHARPIN deficiency. Thus, deregulated TLR3 signalling contributes to dermatitis development in SHARPIN-deficient mice. |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | http://dx.doi.org/10.18725/OPARU-4292Test; 885179099; https://oparu.uni-ulm.de/xmlui/123456789/4331Test; http://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-4331-1Test |
| DOI: | 10.18725/OPARU-4292 |
| الإتاحة: | https://doi.org/10.18725/OPARU-4292Test https://oparu.uni-ulm.de/xmlui/123456789/4331Test http://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-4331-1Test |
| حقوق: | Standard ; https://oparu.uni-ulm.de/xmlui/license_v3Test |
| رقم الانضمام: | edsbas.67E80A24 |
| قاعدة البيانات: | BASE |
| DOI: | 10.18725/OPARU-4292 |
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