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The Role of Rac1 on STAT3-NFkappaB complex in Starved Cancer cells
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 우현구 | - |
| dc.contributor.author | 김성주 | - |
| dc.date.accessioned | 2019-08-13T16:41:24Z | - |
| dc.date.available | 2019-08-13T16:41:24Z | - |
| dc.date.issued | 2019-08 | - |
| dc.identifier.other | 29148 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/15598 | - |
| dc.description | 학위논문(박사)--아주대학교 일반대학원 :의생명과학과,2019. 8 | - |
| dc.description.tableofcontents | I. INTRODUCTION 1 A. Backgrounds 1 B. Purpose 20 II. MATERIALS AND METHODS 22 A. Cells and other reagents 22 B. Plasmids and stable cells 22 C. Rac1 GTPase activation assay 23 D. Primers for real-time PCR 23 E. Western blotting and immunoprecipitation 24 F. Confocal microscopy 25 III. RESULTS 26 A. Activated Rac1 coexistes with STAT3, p65, and IkappaBalpha in nutrient-starved cancer cells 26 B. IkappaBalpha degradation by Rac1, in cancer cells starved by HBSS treatment, is independent of serine phosphorylation of IkappaBalpha by IKK 33 C. Activation of Rac1 is necessary for the translocation into the nucleus and STAT3 and NFkappaB avtivity 45 D. Unphosphorylated STAT3 forms a complex with NFkappaB in cancer cells starved by HBSS 53 E. Rac1 is necessary for translocation into nucleus of the STAT3-NFkappaB complex in cancer cells starved by HBSS treatment 59 IV. DISCUSSION 63 REFERENCES 70 국문요약 75 APPENDIX 77 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | The Role of Rac1 on STAT3-NFkappaB complex in Starved Cancer cells | - |
| dc.title.alternative | Sungjoo Kim | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | Sungjoo Kim | - |
| dc.contributor.department | 일반대학원 의생명과학과 | - |
| dc.date.awarded | 2019. 8 | - |
| dc.description.degree | Doctoral | - |
| dc.identifier.localId | 951958 | - |
| dc.identifier.uci | I804:41038-000000029148 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/common/orgView/000000029148 | - |
| dc.description.alternativeAbstract | Signal transducer and activator of transcription factor 3 (STAT3) and nuclear factor kappa B (NFkB) are activated and interact in several human tumors, but it is not completely clear how the STAT3-NFkB complex is delivered to the nucleus. This study demonstrated that activated Rac1 co-localized with STAT3 and NFkB in cancer cells which had been starved by nutrient depletion. Rac1 induced the degradation of IkBα in cancer cells under nutrient starvation. In contrast, knockdown of Rac1 and overexpression of Rac1N19, as the dominant-negative mutant of Rac1, did not induce IkBα degradation. The degradation of IkBα by Rac1 in starved cancer cells was independent of serine phosphorylation of IkBα by IkB kinase. This demonstrated that the ubiquitin proteasome inhibitor MG132 only increased non-phosphorylated IkBα but did not increase serine-phosphorylated IkB. Knockdown of Rac1 also blocked to translocation of the STAT3-NFkB complex into the nucleus, indicating that activated Rac1 was necessary for this process. In starved cancer cells, STAT3 Y705F, a non-phosphorylated STAT3 mutant, formed a complex with NFkB which was translocated into the nucleus and where the activity of NFkB was induced. These results indicated that nuclear translocation of the STAT3-NFkB complex did not require the phosphorylation of STAT3. This is the first study to show that Rac1 is important in the function of the STAT3-NFkB complex in cancer cells starved by nutrient depletion, indicating that Rac1 is a therapeutic target for cancer treatment. | - |
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- Graduate School of Ajou University > Department of Biomedical Sciences > 4. Theses(Ph.D)
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