Chemical genomic analysis of telomerase regulation mechanisms : small molecules inhibiting human telomerase reverse transcriptase gene in cancer cells = Telomerase 조절 기작에 대한 화학 유전체학적 분석 : 암세포에서 Human telomerase reverse transcriptase 유전자 발현을 억제하는 저분자 화합물small molecules inhibiting human telomerase reverse transcriptase gene in cancer cells

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Human telomerase activity plays an important role in immortality of cells and tumorigenesis. Whereas telomerase activity is tightly repressed in most human normal somatic cells, telomerase activity is activated in most human cancer cells. Major factor that determines the telomerase activity is known to be the expression of its catalytic subunit, human telomerase reverse transcriptase (hTERT) gene. Here I would demonstrate that novel factors may be involved in telomerase regulations and offer the starting point for the study of telomerase regulation pathway through chemical genomic approach. I mentioned that telomerase activity is regulated by the expression of its catalytic subunit, hTERT gene. From this fact, I identified small molecules inhibiting the hTERT gene expression in human cancer cells from screening procedure of selected set of chemical libraries after development of assay system for hTERT gene expression. Next, I studied the small molecules’ action mechanism on the basis of the fact that Sp1 and HDAC2 are important factors in regulating the hTERT gene expression. So I performed the experiments to confirm whether identified small molecules inhibit the hTERT gene expression by affecting the Sp1 and whether HDAC is involved in this inhibition process. The results of the experiments suggested the possibility that small molecules might induce Sp1 modification and this modification might inhibit the hTERT gene expression by increasing the interaction between Sp1 and HDAC2 and increasing the recruitment of HDAC2 onto the hTERT promoter. I demonstrated that identified two small molecules induced the Sp1 phosphorylation. Finally, I suggest the action mechanism model of identified small molecules like this: first, identified small molecule binds to its target proteins and affects their function in the cell. This induces the signal transduction to the next components and finally inhibits the hTERT gene expression. Thus, identifying the target proteins of t...
Kim, Tae-Kookresearcher김태국researcher
한국과학기술원 : 생명과학과,
Issue Date
243524/325007  / 020033414

학위논문(석사) - 한국과학기술원 : 생명과학과, 2005.2, [ v, 50 p. ]


Telomerase Regulation Mechanismsneurite branching; cell adhesion a strategy enabling a high throughput analysis of SUMO conjugation; 신경돌기 형성; Kal-1; Telomerase 조절 기작1

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