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標題: | TRAF3 與 SUMO 相關分子間交互作用之研究 Studies on the interaction between TRAF3 and SUMO-associated molecules |
作者: | Han-Jen Chang 張瀚壬 |
指導教授: | 陳俊任(Chun-Jen Chen) |
共同指導教授: | 張世宗(Shih-Chung Chang) |
關鍵字: | SUMO 化修飾系統,SUMO E3 黏合酶,TRAF3,TLR3路徑, SUMO,SUMO E3 ligase,TRAF3,TLR3 pathway, |
出版年 : | 2011 |
學位: | 碩士 |
摘要: | Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and play important roles in the innate immune response. Signaling of most TLRs require the adaptor molecule MyD88, except for TLR3 which signals through TRIF. Upon binding of virus-derived double-stranded RNAs, TLR3 initiates a signaling cascade involving TRIF, TRAF3, TBK1 and IKKε, resulting in the phosphorylation and nuclear translocation of IRF3 which activates the transcription of type I interferons. Among these signaling molecules, IKKε and IRF3 are reported to be modified by the small ubiquitin-like modifier (SUMO). Since TRAF3 also contains several consensus sites of SUMOylation, we initiated this study to determine whether TRAF3 is also modified by SUMO. Co-immunopreciptation experiments show that TRAF3 is associated with SUMO1; however, the SUMO1-associated TRAF3 has no increase in molecular weight that corresponds to SUMO1 conjugation, raising the possibility that TRAF3 interacts with SUMO1 in a non-covalent way. Experiments using TRAF3 deleted of N-terminus or C-terminus show that the N-terminal half of TRAF3 is responsible for SUMO1 association. Further truncational analysis indicates that the N-terminal RING domain plays a critical role for the interaction. We also found that TRAF3 is associated with Ubc9 (the SUMO conjugating enzyme) in a RING domain-dependent manner. Moreover, overexprssion of TRAF3 enhances SUMOylation of an unidentified protein of around 130 kDa. These results suggest that TRAF3 may act as a SUMO E3 ligase. Studies are underway to elucidate the mechanism of the interaction between SUMO and TRAF3. Further investigations on how SUMOylation affects TRAF3 function and signaling should provide more insights into how the TLR3 pathway is regulated during an antiviral response. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33007 |
全文授權: | 有償授權 |
顯示於系所單位: | 生化科技學系 |
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