Screening of small molecule modulators of the p53 pathway with BioMAGICBioMAGIC을 이용한 p53 Pathway의 저분자 화합물 조절인자의 Screening에 대한 연구

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dc.contributor.advisorKim, Tae-Kook-
dc.contributor.advisor김태국-
dc.contributor.authorKim, Tae-Uk-
dc.contributor.author김태욱-
dc.date.accessioned2011-12-12T08:54:47Z-
dc.date.available2011-12-12T08:54:47Z-
dc.date.issued2006-
dc.identifier.urihttp://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=260022&flag=dissertation-
dc.identifier.urihttp://hdl.handle.net/10203/28081-
dc.description학위논문(석사) - 한국과학기술원 : 생명과학과, 2006.8, [ v, 34 p. ]-
dc.description.abstractIt is important to screen bioactive compounds including drugs inside living human cells under physiologically and pharmacologically relevant contexts. BioMAGIC can be used to monitor protein-protein interactions as well as small molecule-protein interactions. In this study, I examined whether BioMAGIC can be used to screen small molecule modulators of specific protein-protein interaction such as p53-MDM2 interaction in vivo inside living cells. One of the most potent small molecule inhibitors identified in this screen was CGK360. Treatment with CGK360 markedly reduced the magnetic field-directed translocation of $EGFP-p53^*$ in both RKO and U2OS cells. To examine how CGK360 inhibits p53-MDM2 interaction, we examined the effect of CGK360 on p53 and MDM2 protein levels by immunoblotting. Incubation of RKO cells with CGK360 led to increase in the levels of p53 and its target proteins including MDM2 and $p21^{Waf/Cip1}$. These results raise a possibility that p53 accumulates in cells treated with CGK360, thus leading to an elevation in the levels of MDM2 and $p21^{Waf/Cip1}$ in a manner consistent with activation of th p53 pathway. To address this possibility, I analyzed the subcellular localization fo p53 in RKO cells after treatment with CGK360. Treatment with CGK360 resulted in the dramatic accumulation of p53 protein inside of nucleus. To confirm the p53 activation by CGK360, I measured the DNA binding activity and phosphorylation of p53 after treatment with CGK360. The p53 DNA binding activity was assessed by an electrophoretic mobility shift assay. Treatment with CGK360 sharply induced the formation of p53-DNA complex. Immunoblotting showed that CGK360 induced the phosphorylation of p53 on serine residue Ser15, an event which is critical to the process of p53 activation. All of these results consistent with the idea that CGK360 is an activator of the p53 pathway. CGK360 is flat, which may allow it to intercalate between the stacking bases of DNA. Th...eng
dc.languageeng-
dc.publisher한국과학기술원-
dc.subjectin vivo-
dc.subjectsmall molecule-
dc.subjectp53-
dc.subjectBioMAGIC-
dc.subjectscreening-
dc.subject상호작용-
dc.subject세포 내-
dc.subject바이오매직-
dc.subject스크리닝-
dc.subject저분자 화합물-
dc.titleScreening of small molecule modulators of the p53 pathway with BioMAGIC-
dc.title.alternativeBioMAGIC을 이용한 p53 Pathway의 저분자 화합물 조절인자의 Screening에 대한 연구-
dc.typeThesis(Master)-
dc.identifier.CNRN260022/325007 -
dc.description.department한국과학기술원 : 생명과학과, -
dc.identifier.uid020043162-
dc.contributor.localauthorKim, Tae-Kook-
dc.contributor.localauthor김태국-
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BS-Theses_Master(석사논문)
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