DC 欄位 | 值 | 語言 |
dc.contributor | 醫學院: 免疫學研究所 | zh: |
dc.contributor | 指導教授: 賴明宗 | zh |
dc.contributor.author | 徐子勝 | zh |
dc.contributor.author | Hsu, Tzu-Sheng | en |
dc.creator | 徐子勝 | zh |
dc.creator | Hsu, Tzu-Sheng | en |
dc.date | 2014 | - |
dc.date.accessioned | 2017-03-03T01:00:00Z | - |
dc.date.accessioned | 2018-07-09T01:52:41Z | - |
dc.date.available | 2017-03-03T01:00:00Z | - |
dc.date.available | 2018-07-09T01:52:41Z | - |
dc.date.issued | 2014 | - |
dc.identifier.uri | http://ntur.lib.ntu.edu.tw//handle/246246/273106 | - |
dc.description.abstract | E3泛素連接酶對於誘發及維持T細胞去活化 (T cell anergy) 扮演重要的角色。誘發T細胞去活化過程中,去活化相關的E3泛素連接酶如Cbl-b, Itch和GRAIL的蛋白質表達量會上升,並透過降解T細胞活化訊息傳遞分子PKCθ和PLCγ1而抑制T細胞再活化。然而這些去活化相關的E3泛素連接酶如何彼此協同,進而維持T細胞去活化卻未完全清楚。 本篇研究中,我們探討Notch相關E3泛素連接酶deltex1 (DTX1) 在維持T細胞去活化的扮演的角色。我們發現,DTX1會結合PKCθ和PLCγ1並抑制其蛋白質表現。進一步的研究顯示,相似Cbl-b和Itch的作用,DTX1催化PKCθ單體泛素化,使得單體泛素化的PKCθ經由核內體-溶小體 (endosome-lysosome) 途徑而分解,處理蛋白酶體抑制劑並不會降低DTX1所調控PKCθ降解。此外,我們也觀察到DTX1會與Cbl-b結合並促進Cbl-b的表現。進一步的實驗證實,DTX1抑制PKCθ主導的Cbl-b降解並增加Cbl-b的蛋白質穩定。本篇的研究闡述了去活化相關的E3泛素連接酶在T細胞去活化中的協同作用:DTX1泛素化PKCθ並經由核內體-溶小體 (endosome-lysosome) 途徑調控PKCθ降解;DTX1透過調控PKCθ降解促進Cbl-b蛋白質穩定;DTX1與Cbl-b共同作用確保PKCθ的活性完全抑制。 | zh |
dc.description.abstract | Ubiquitin E3 ligases are associated with induction and maintance of T cell anergy. These E3 ligases, including Cbl-b, Itch, and GRAIL, attenuate T cell activation by targeting to signaling molecules such as PKCθ and PLCγ1 for degradetion. How these anergy-associated E3 ligases coordinate during T cell anergy remains incompletely understood. In this study, we found that Notch-related E3 ligase deltex1 (DTX1) also regulated the expression of PKCθ and PLCγ1. DTX1 interacted with PKCθ and PLCγ1 and promoted the degradation of PKCθ and PLCγ1. T cell anergy-induced downregulation of PKCθ was prevented in Dtx1-/- T cells, supporting the essential role of DTX1 in PKCθ downregulation. DTX1 promoted monoubiquitination of PKCθ, similar to Cbl-b and Itch. DTX1-directed PKCθ degradation was not prevented by proteasome inhibitor, but instead DTX1 directed the re-localization of PKCθ into the lysosomal pathway. In addition, DTX1 interacted with Cbl-b and increased the protein levels of Cbl-b. We further demonstrated that, through the downregulation of PKCθ, DTX1 prevented PKCθ-induced Cbl-b degradation and increased Cbl-b protein stability. Our results illustrate the coordination between E3 ligases during T cell anergy; DTX1-mediated PKCθ degradation further stabilizes Cbl-b and DTX1 acts with Cbl-b to assure a more completely silencing of PKCθ. | en |
dc.format.extent | 7353927 bytes | - |
dc.format.mimetype | application/pdf | - |
dc.language | zh | - |
dc.rights | 論文公開時間: 2018/3/12 | zh |
dc.rights | 論文使用權限: 同意有償授權(權利金給回饋學校) | - |
dc.subject | T細胞去活化 | zh |
dc.subject | E3泛素連接? | zh |
dc.subject | Anergy | en |
dc.subject | E3 ubiquitin ligase | en |
dc.subject | deltex1 | en |
dc.subject | PKCθ | en |
dc.title | Deltex1在T細胞去活化機制調控之探討 | zh |
dc.title | Study on the Molecular Mechanism of Deltex1 in T cell Anergy | en |
dc.type | thesis | en |
dc.identifier.uri.fulltext | http://ntur.lib.ntu.edu.tw/bitstream/246246/273106/1/ntu-103-D97449003-1.pdf | - |
item.fulltext | with fulltext | - |
item.grantfulltext | open | - |
item.openairetype | thesis | - |
item.openairecristype | http://purl.org/coar/resource_type/c_46ec | - |
item.cerifentitytype | Publications | - |
顯示於: | 免疫學研究所
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