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dc.contributor.advisor이수영-
dc.contributor.author정으뜸-
dc.creator정으뜸-
dc.date.accessioned2016-08-26T12:08:45Z-
dc.date.available2016-08-26T12:08:45Z-
dc.date.issued2012-
dc.identifier.otherOAK-000000072255-
dc.identifier.urihttps://dspace.ewha.ac.kr/handle/2015.oak/190970-
dc.identifier.urihttp://dcollection.ewha.ac.kr/jsp/common/DcLoOrgPer.jsp?sItemId=000000072255-
dc.description.abstractTNF receptor-associated factor 6 (TRAF6) is an essential E3 ligase for the activation of MAP kinase and NF-κB in signal transductions. TRAF6 functions with ubiquitin conjugating enzyme to mediate Lys 63-linked polyubiquitination chains that activate TAK1 kinase complex. Activated TAK1 then phosphorylates downstream factors, IKK and NF-κB which play a central role in several inflammatory signaling pathways. Particularly, TRAF6 is known to be critical for RANKL-mediated osteoclastogenesis which is important for skeletal homeostasis maintenance. A novel RANKL-inducible gene, early estrogen-induced gene 1 (EEIG1) was identified by gene chip and revealed that it plays an important role in osteoclastogenic signaling by binding to RANK. However, its functional mechanism is poorly understood. In this study, I show that EEIG1 interacts with TRAF6 and Lys 63-linked polyubiquitination of EEIG1 is activated by TRAF6. Furthermore, EEIG1 interacts with TAK1 and increases phosphorylation of TAK1, in turn activates IKK. Likewise, EEIG1 increases TRAF6-induced NF-κB activation. Thus, these results indicate that EEIG1 may serve as an important modulator for TRAF6-associated NF-κB pathway.;TRAF6는 TNFR에 관여하는 단백질로 MAPK와 NF-κB의 신호전달에서 중요한 전이효소로 작용한다. TRAF6의 Lys 63-유비퀴틴 활성작용은 RANKL에 의한 파골세포의 분화와 기능에서 하위 신호전달계를 활성화 시키는 역할을 한다. EEIG1은 gene chip 기술을 이용하여 찾은 RANKL에 의해 유도되는 유전자로, 아직까지 그 기능은 밝혀지지 않았다. TRAF6와 EEIG1의 deletion construct를 이용하여 실험한 결과, EEIG1의 NH2-terminal 특정 부분이 TRAF6와 결합하며 TRAF6의 Lys 63-유비퀴틴 활성을 대신 증폭시킨다는 것을 알 수 있었다. 또한 TRAF6의 하위 신호전달계의 중심으로 알려진 TAK1과도 결합하여 TAK1을 크게 활성화시키는 것을 알 수 있었다. EEIG1은 TAK1의 활성뿐 아니라 세포 내 염증, 활성, 면역반응의 궁극적인 인자로 작용하는 NF-κB의 활성도 증가시켰다. 이러한 결과는 EEIG1의 유비퀴틴 활성이 RANKL 신호체계와 더불어 파골세포의 분화 기작을 이해하는데 중요한 역할을 하리라는 것을 시사한다.-
dc.description.tableofcontentsI. INTRODUCTION 1 II. EXPERIMENTAL PROCEDURES 4 1. Generation of osteoclast precursor cells 4 2. Construction of truncated mutants and mutagenesis 4 3. Construction of 293T cells expressing RANK 5 4. Immunoprecipitation (IP) 6 5. GST pull down assay 6 6. Western blot analysis 7 7. Reporter assay 8 8. Reverse transcription and quantitative real-time PCR 8 III. RESULTS 10 1. EEIG1 was selectively expressed by RANKL stimulation. 10 2. TRAF6 interacts with EEIG1 in a specific region of TRAF-C domain 13 3. TRAF6-biding sites within EEIG1 are located in the NH2-terminal region 16 4. Lys 63-linked polyubiquitination engages between TRAF6 and EEIG1 20 5. Interaction between EEIG1 and TAK1 mediates TAK1 phosphorylation 24 6. EEIG1 is involved in RANKL induced NF-κB activation 27 IV. DISCUSSION 30 V. REFERENCES 34 VI. 논문개요 38-
dc.formatapplication/pdf-
dc.format.extent1057729 bytes-
dc.languageeng-
dc.publisher이화여자대학교 대학원-
dc.subject.ddc600-
dc.titleEEIG1 ubiquitination promotes NF-κB activation in RANKL signaling-
dc.typeMaster's Thesis-
dc.title.translatedRANKL 신호체계에서 NF-κB 활성에 미치는 EEIG1의 역할-
dc.format.pageiv, 39 p.-
dc.identifier.thesisdegreeMaster-
dc.identifier.major대학원 생명·약학부생명과학전공-
dc.date.awarded2012. 8-
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