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Chemical Genetic Screening and Action Mechanism of p53-Activating Small Molecules as Potential Antitumour Agents

등록일
2005년 8월 11일 11시 04분 53초
접수번호
0749
발표코드
24P129포 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
발표시간
금 <발표Ⅰ>
발표형식
포스터
발표분야
생명화학
저자 및
공동저자
박상은, 이우길, 민용기, 김범태
한국화학연구원,
The p53 tumor suppressor protein functions as a key component to protect cells from malignant transformation. To understand the p53 regulatory pathway using chemical genetic approach we developed triple readout assay systems consisting of two stable cell lines, RKO-(p53)-FL and RKO-(p53)-SEAP for p53 activity, and SV40-RL for internal control, respectively. These reporter cell lines were mixed in a single well of 384-well plates and assayed for KRICT chemical library of about 8,500 compounds in combination with and without the potent DNA damaging agent, Doxorubicin. As a result from HTS screening, several compounds were found to activate the p53-mediated transcriptional activity. These chemical compounds potentially induced the p53 phosphorylation, p53-dependent target gene expression and cell cycle arrest. Now we are attempting to elucidate the action mechanisms of these compounds in p53 signaling pathway. Our data suggest that this cell-based assay system provides the useful tool to screen and study the potential therapeutic agent to modulate the p53 signaling pathway.

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